They refer to a partial seizure that is followed by loss of level of consciousness, so strictly speaking it would be a symptomatic complex partial seizure, not a secondarily generalized partial seizure (which occurs when tonic-clonic movements extend to the rest of the extremities). For this reason the most correct option would be two because it does not specify that it is a simple symptomatic partial seizure, but leaves open the possibility that it is a simple or complex symptomatic partial seizure.

They refer to a partial seizure that is followed by loss of level of consciousness, so strictly speaking it would be a symptomatic complex partial seizure, not a secondarily generalized partial seizure (which occurs when tonic-clonic movements extend to the rest of the extremities). For this reason [HIDDEN] because it does not specify that it is a simple symptomatic partial seizure, but leaves open the possibility that it is a simple or complex symptomatic partial seizure.

A 39-year-old man who in the last 3 months has had two episodes of wide and involuntary jumping movements of the left limbs, which in about two minutes lead to loss of consciousness. In the neuroradiological study a right frontal expansive lesion suggestive of cerebral glioma was found.How would you classify this patient's epilepsy?

Partial secondarily generalized symptomatic.

[Rare cases of reflex epilepsy in patients with gliomas of the left hemisphere].

We present the cases of symptomatic reflex epilepsy in patients with left hemisphere tumors. The first case: a 23-year-old man has had tonic-clonic seizures of the tongue with rare secondary localization over the past several months. The seizures were caused by intense tongue movements, in particular rightward and leftward (when having chewing gum or a candy in his mouth), but not during speech production or eating. MRI scanning detected a small tumor in the lower segments of the central gyrus. It was found during the surgery under electrophysiological control that the tumor (Gr II astrocytoma) resided in the zone corresponding to the right half of the tongue and included this zone. The tumor was partially resected. The second patient, a 52-year-old man, has been suffering from generalized seizures since 1998. The seizures were caused by intense verbal load, in the beginning of spontaneous speech and subsequently when the patient was listening to others' speech or was writing. Spontaneous seizures emerged when the patient stopped taking his anti-seizure medications unilaterally. MRI showed glioma in the posterior segments of the left temporal lobe. The patient underwent radiation and chemotherapy. In 2013, the patient's condition worsened (right-sided hemiparesis and severe speech impairment emerged); the tumor was partially resected and an extensive cyst was opened. The third patient, a 38-year-old man with Gr III astrocytoma in the left insula with past medical history of spontaneous vegetative seizures, had only a seizure anticipation caused by strong smells. All the patients were prescribed chemo-, radiation, and anti-seizure therapy.

[A case of temporal lobe epilepsy with recurrent dysphasic seizures].

We reported a 40-year-old right-handed female with temporal lobe epilepsy manifesting recurrent dysphasic seizures. At age 25, the patient developed a complex partial seizure, who subsequently showed frequent auditory seizures that often evolved to complex partial or secondarily generalized seizures at age 25-27, and dysphasic seizures (DSs) at age 27 -40. DSs were characterized by total aphasia without impairment of consciousness, which were often accompanied by functional hallucination. Brain CT, cerebral angiography, and brain MRI demonstrated no abnormal findings. At age 39 (May 20, 1989), recurrent aphasic state was unexpectedly observed during medical examinations. An EEG was performed immediately, and the EEG seizure pattern (duration: ca. 8-17 sec) in which 15 -16 Hz spikes began in the left posterior temporal region and spread rapidly to the left midtemporal, inferior frontal, and central regions was detected 14 times within 30 minutes. During the seizure patterns, the patient was aphasic.

Case report. Gelastic seizures in a patient with right gyrus cinguli astrocytoma.

Gelastic seizure (GS) also known as "gelastic epilepsy" is a rare type of seizure associated with several different conditions such as tumors--hypothalamic hamartromas, tuberous sclerosis, hemangiomas, post infectious foci, cortical temporal dysplasia. We report one case of this rare condition generated by a right gyrus cinguli gr. II astrocytoma. A 27 year-old male, right handed, was admitted for a 2 years history of very frequent gelastic seizures accompanied sometimes by simple motor partial seizures in both arms, more often being involved his left arm, without impairment of his consciousness state. His neurological examination was normal. Diagnosis was made on native CT scan: minimal hypodense frontal right paramedian lesion, cerebral MRI showed a small well delimited right, parenchymal, homogeneous lesion (16/22/15 mm), involving gyrus cinguli, without perilesional edema and mass effect, hyperintense both on T1 and T2 MR sequences, non-enhancing after Gadolinium. The cerebral lesion was also documented on EEG and video-EEG recordings. Using an interhemispheric microsurgical approach, above the corpus callosum and the right pericallosal artery, at the level of gyrus cinguli, a yellow-gray, infiltrative tumor, having a moderate vascularisation, has been identified and totally removed. The anatomopathological analysis revealed a grade II astrocytoma. The patient recovered very well, without deficits, no gelastic seizures or epileptic manifestations; three months after operation he is still free of seizures. A case of gelastic seizures accompanied by simple motor partial seizures in both arms, without the impairment of his consciousness state induced by a grade II right gyrus cinguli astrocytoma is described and documented by radiological and electrophysiological studies. Using microsurgical resection, the tumor was totally removed, the patient clinical condition improved. Without an affective connotation as in temporal or hypothalamus topography, gelastic seizures are not patognomonic for hypothalamic hamartomas and in the case of frontal localization of the lesion; they can be associated with motor involvement of the limbs as in our case.

Frontal lobe epilepsy

Tonic posture and clonic movements are common symptoms among most of the areas of the frontal lobe, therefore the type of seizures associated with frontal lobe epilepsy are commonly called tonic-clonic seizures. Dystonic motor movements are common to both TLE and FLE, but are usually the first symptom in FLE episodes where they are quite brief and do not affect consciousness. The seizures are complex partial, simple partial, secondarily generalized or a combination of the three. These partial seizures are often misdiagnosed as psychogenic seizures. Semiology A wide range of more specific symptoms arise when different parts of the frontal cortex are affected.

Epilepsy syndromes

Lennox-Gastaut syndrome Lennox-Gastaut syndrome (LGS) is a generalized epilepsy that consists of a triad of developmental delay or childhood dementia, mixed generalized seizures, and EEG demonstrating a pattern of approximately 2 Hz "slow" spike-waves. Onset occurs between two and 18 years. Epilepsy is consider a chronic (meaning it lasts for a long time) condition that is defined by seizures. Lennox-Gastaut syndrome (LGS) is a rare and severe form of epilepsy. As in West syndrome, LGS result from idiopathic, symptomatic, or cryptogenic causes, and many patients first have West syndrome. Authorities emphasize different seizure types as important in LGS, but most have astatic seizures (drop attacks), tonic seizures, tonic-clonic seizures, atypical absence seizures, and sometimes, focal seizures. Anticonvulsants are usually only partially successful in treatment.

Seizure types

In 1997, the ILAE began work on revising the classification of seizures, epilepsies and epileptic syndromes. This revision remains in gestation and has not superseded the 1981 classification. Proposed changes to terminology include: Replace partial with the older term focal to describe seizures that originate in one part of the brain (though not necessarily a small or well defined area). The word partial was regarded as ambiguous. Drop the terms simple partial and complex partial - grouping based on the effect to consciousness is no longer regarded as useful. Replace cryptogenic with probably symptomatic. The hierarchy presented has the structure:

Partial Epilepsy -- Introduction

The 2017 International League Against Epilepsy classification of seizures makes a point of the onset/origin of the seizure in the brain. [3] Seizures can be categorized as partial or generalized. Seizures originating from a single location in the brain are considered to have a focal onset, known as a partial seizure. Seizure activity originating simultaneously from bilateral hemispheres is considered to have a generalized onset. Partial seizures are further divided into simple and complex. Simple partial seizures involve a small portion or a focal area of the brain. Complex partial seizures start in one area and travel to another. The main difference between a simple partial seizure and a complex partial seizure is impaired awareness and a post-ictal period in the latter, which also occurs in a generalized seizure. Thus complex partial seizures and generalized seizures may have similar presentations; however, they differ in that generalized seizures involve both hemispheres of the brain, whereas complex partial seizures travel from one focal area to another. Focal epilepsy and partial epilepsy are used interchangeably.

[Cerebral lesions following convulsive partial status epilepticus. Clinical, neuroradiologic and PET study of a case].

An 11-year-old girl developed signs of intracranial hypertension after status epilepticus with convulsive movements of her right upper limb. Computerized tomography revealed left hemispheric hypodensity with mass effect, attributed to vasogenic edema. Intracranial hypertension was controlled under intracranial pressure monitoring and clinical status slowly improved. The patient was aphasic and right hemiplegic when she recovered consciousness but she remarkably recovered from her neurological deficits during the following two years despite neuroradiological evolution demonstrating extensive destruction of the left cortex and white matter. Two positron emission tomography (PET) scans were performed respectively six weeks and eight months after status epilepticus, and both demonstrated profound left hemispheric hypometabolism except in the lenticular nucleus and a restricted area of motor/premotor cortex. On the other hand, glucose metabolism in the right hemisphere was heterogeneously increased on the second PET when compared with the first PET. We concluded that, in this case, clinical recovery might have implicated functional reorganization arising from the intact hemisphere.

Neurology_Adams

Focal motor seizures are attributable to a discharging lesion of the frontal lobe. A common type, originating in the supplementary motor area, takes the form of a turning movement of the head and eyes to the side opposite the irritative focus, often associated with a tonic extension of limbs, also on the side contralateral to the affected hemisphere. This may constitute the entire seizure, or it may be followed by generalized clonic movements. The extension of the limbs may occur just before or simultaneously with loss of consciousness but a lesion in one frontal lobe may give rise to a major generalized convulsion without an initial turning of the head and eyes. It has been postulated that, if there is loss of consciousness, it is the result of a rapid spread of the discharge from the frontal lobe to integrating centers in the thalamic or high midbrain reticular formation.

Frontal lobe epilepsy

Epidemiology Epilepsy is a relatively common disorder, affecting between 0.5-1% of the population, and frontal lobe epilepsy accounts for about 1-2% of all epilepsies. The most common subdivision of epilepsy is symptomatic partial epilepsy, which causes simple partial seizures, and can be further divided into temporal and frontal lobe epilepsy. Although the exact number of cases of frontal lobe epilepsy is not currently known, it is known that FLE is the less common type of partial epilepsy, accounting for 20-30% of operative procedures involving intractable epilepsy. The disorder also has no gender or age bias, affecting males and females of all ages. In a recent study, the mean subject age with frontal lobe epilepsy was 28.5 years old, and the average age of epilepsy onset for left frontal epilepsy was 9.3 years old whereas for right frontal epilepsy it was 11.1 years old.

[Epileptic seizures as initial symptom of intracranial tumors. A prospective study in adults].

A prospective study of 125 patients with late-onset epileptic crisis: Group G I with 65 cases between 20 and 50 years of age, and Group G II, including 60 patients older than 50 years at the time of the first crisis. Brain tumors were diagnosed in fourteen cases, four (6.1%) in G I and ten (16.6%) in G II. In decreasing order of frequency, the ictal pattern was tonic-clonic, status epilepticus, partial simple, partial complex and "drop-attacks". The lesions were located as follows:frontal in seven subjects, parietal in four, multiple in two and temporo-basal in one. Histologically, the tumors were three meningiomas, two gliomas, one astrocytoma, and three metastatic lesions. These findings agree with those of other series, in terms of predominant type of crisis, site and histologic type; but they differ in the age of first symptoms, and in the fact that tumors occupy only a third place as cause of epileptic crisis.

[Epilepsies during the first year of life].

An important number of epileptic patients who began with epileptic seizures during the first year of life have not just been well classified. The objective is to identify the different types of epilepsies and epileptic seizures which begin during the first year of life, according to the last classification of epilepsy and epileptic syndromes of 1989. We have studied 471 patients who consulted to our service in the last 5 years, with epileptic seizures during the first year of life. We excluded neonatal seizures and febrile convulsions. 1. Partial epilepsy: a) idiopathic: 12 (2.5%); b) symptomatic: 130 (28%); c) cryptogenic: 25 (5%). 2. Generalized epilepsy: a) idiopathic: benign myoclonic epilepsy in infancy, 6 (1%); b) cryptogenic-symptomatic: symptomatic West syndrome, 155 (33%); cryptogenic West syndrome, 65 (14%); cryptogenic myoclonic epilepsy, 6 (1%); early infantile epileptic encephalopathy, 8 (1.6%); early myoclonic encephalopathy, 4 (0.8%); other symptomatic generalized epilepsies without specific aetiology, 14 (3%). 3. Epilepsies and syndromes undetermined as to whether they are focal or generalized: a) severe myoclonic epilepsy in infancy, 15 (3%); symptomatic epilepsy with multifocal and independent spikes, 3 (0.6%); other undetermined epilepsies not defined above, 3 (0.6%). 4. Special syndromes: occasional convulsions, 15 (3%). West syndrome is the commonest type of epilepsy during the first year of life, particularly symptomatic West syndrome. Symptomatic partial epilepsies are in the second place in frequency. We identified 12 patients with idiopathic partial epilepsy, who full-filled clinical and EEG characteristics of a recently described epilepsy: benign infantile familial convulsions. The study showed the predominance of symptomatic epilepsy, generalized (represented by West syndrome) and partials. Finally 6% of the patients have a generalized epilepsy, cryptogenic or symptomatic, not defined in the classification.

[Consciousness disorders in focal lesions of the right and left cerebral hemispheres].

In the light of modern concepts of functional asymmetry in the human brain, the authors analyse paroxysmal conditions of changed consciousness which occurred in 160 patients with lesions of the hemispheres due to brain tumors (75 patients) and in epilepsy (85 patients). It is shown that certain forms of changed consciousness are characteristic of disorders of the right and left hemispheres in right-handedness. This clinical fact is taken as a basis for the assumption that in the formation of consciousness both hemispheres in different ways play a certain role and they provide different "formating" kinds of consciousness: the right hemisphere--a direct perception or a sensory perception of the environment and itself, the left--process of abstract perception based on speech, symbols, semantics.

Neurology_Adams

As indicated earlier, the International Classification divides all seizures into two types—generalized, in which the clinical and EEG manifestations indicate bilateral and diffuse cerebral cortical involvement from the onset, and focal, in which the seizure is often the product of a demonstrable focal lesion or EEG abnormality in some part of the cerebral cortex. The manifestations of focal seizures reflect the locale of the lesion. In the past focal seizures were classified by whether consciousness was retained (partial) or impaired (complex), but are now subsumed under the term “dyscognitive” if awareness is altered. Focal seizures with sensory or motor features at the onset most often arise from foci in the sensorimotor cortex. Those with impairment of consciousness, which occurs in many forms, most often have their focus in the limbic and autonomic areas or in the temporal lobe, but a frontal localization is also known. Table 15-2 lists the common sites of the lesions and the

Generalized nonconvulsive status epilepticus in symptomatic partial epilepsy.

A 6-year-old male with cortical dysplasia who developed secondarily generalized nonconvulsive status epilepticus is reported. He had partial epilepsy since the age of 10 months. On electroencephalography, almost continuous left frontocentral/anterior temporal spikes were observed at 3 years of age, which lasted until 6 years of age, when he developed nonconvulsive status epilepticus. Nonconvulsive status epilepticus lasted for more than 7 days. Electroencephalography during nonconvulsive status epilepticus documented almost continuous generalized polyspike-wave complexes suggestive of generalized nonconvulsive status epilepticus. On magnetic resonance imaging, abnormal gyration was observed in the left frontal lobe. Histopathologic analysis of the resected left frontal lobe revealed cortical dysplasia. The present case demonstrates that continuous focal epileptiform discharges caused by cortical dysplasia in the frontal lobe can develop into secondarily generalized nonconvulsive status epilepticus.

[Gyratory epileptic seizures. Radioclinical correlations].

The authors report 3 cases of gyratory seizures whose epileptic nature was demonstrated on the following features. They appeared with a loss of consciousness. In 2 cases, they ended with a tonic-clonic generalized fit and in the 3 cases, they were mixed with other generalized seizures. From an etiological point of view, in 2 cases, a deep lesion was discovered, the first one near the paracentral lobule, the second in the para-thalamic area. The third one was an idiopathic generalized epilepsy on clinical and electroencephalographic grounds. These 3 cases focus on the difficulties to classify gyratory seizures that may appear in 2 opposite situations, namely in symptomatic partial epilepsy and in idiopathic generalized epilepsy.

Epilepsy syndromes

West syndrome West syndrome is a triad of developmental delay, seizures termed infantile spasms, and EEG demonstrating a pattern termed hypsarrhythmia. Onset occurs between three months and two years, with peak onset between eight and nine months. West syndrome may arise from idiopathic, symptomatic, or cryptogenic causes. The most common cause is tuberous sclerosis. The prognosis varies with the underlying cause. In general, most surviving patients remain with significant cognitive impairment and continuing seizures and may evolve to another eponymic syndrome, Lennox-Gastaut syndrome. It can be classified as idiopathic, syndromic, or cryptogenic depending on cause and can arise from both focal or generalized epileptic lesions. See also Management of drug-resistant epilepsy References Epilepsy Syndromes

Primary central nervous system plasmablastic lymphoma presenting in human immunodeficiency virus-negative but Epstein-Barr virus-positive patient: a case report.

We report a 32-year-old Outer Mongolian man, with plasmablastic lymphoma (PBL) primarily occured in the central nervous system and diagnosed by surgical resection. This patient appeared headache and magnetic resonance imaging (MRI) showed multiple lesions in the right cerebral hemisphere including the right frontal-parietal lobe and right basal ganglia and the left cerebellum, he was diagnosed as lymphoma by stereotactic biopsy in January 2009 in local hospital, and was given radiotherapy 33 times after the biopsy. The patient was admitted to The Military General Hospital of Beijing PLA., Beijing, P.R. China on March 9th, 2011, with chief complaints of right limbs convulsioned suddenly, then fell down and lose of his consciousness, then awoke after 4 to 5 minutes, with symptoms of angulus oris numbness and the right upper limb powerless ten days ago.MRI of the brain revealed a well-defined hyperdense and enhancing mass in the left frontal-parietal lobe, the meninges are closely related, there was extensive peritumoural edema noted with pressure effects, as evident by effacement of the left lateral ventricles and a 0.5 cm shift of the midline to the right side.Surgical resection showed markedly atypical, large singly dispersed or cohesive proliferation of plasmacytoid cells with frequent abnormal mitoses and binucleation, some neoplastic cells were large with round or oval nuclei and showed coarse chromatin and smaller or unapparent nucleoli, some neoplastic cells with prominent nucleoli, apoptosis and necrosis were often presented. Immunohistochemistry staining and gene rearrangement together with other supportive investigation confirmed the diagnosis of primary central nervous system plasmablastic lymphoma. A month later, he was started on chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, leurocristime and prednisone) for a week. Other supportive treatment was provided for symptomatic epilepsy. The patient regained muscle strength in both upper limbs and right lower limb and the symptomatic epilepsy was controlled after two weeks. Then the patient was discharged. Follow-up data shows the patient to be alive eleven months after discharge. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1649317674697046.

[Seizures after the age of sixty (author's transl)].

Three percent of epileptic patients have their first seizure after the age of 60. More than at other ages, the real nature of such fits is very difficult to assert. Most of the reversible attacks occurring at this age are not of grave nature, syncopes are much more frequent. Some semeiological aspects are discussed. Focal seizures are more frequent after the age of 60. Absence status may be the first epileptic symptom in some rare cases (almost all of them being women). 100 patients whose ages ranged from 60 to 83 years, were examined after their first seizure and aetiological problems were examined. The following topics are discussed:--The possible onset of a primary epilepsy, extremely rare at that age;--The incidence of neoplasms, not exceeding 10% for patients whose late onset epilepsy is still an isolated symptom, and who have not been selected from specialized neurological or neurosurgical hospital departments;--The role of vascular epilepsy; in a very few cases, but of great practical interest, the epilepsy may announce a cerebrovascular accident which will occur later. It is, however, difficult to specify the vascular origin of a certain number of temporary unexplained late onset epilepsies. Some other aetiological factors are taken into account: antecedents of trauma, alcoholism, and dementia. The authors agree that in 50% of the cases the aetiology is not obvious. In this group of unknown aetiology it seemed interesting to isolate the following electroclinical form;--Epilepsy grand mal, with apparently generalized seizures; no special pathological antecedents; the neuropsychological and neurological examinations are normal, showing no intellectual disorders; the EEG generally shows slight modifications: quick rhythms, some sharp waves; a global cerebral atrophy is seen by the scanner. Such patients have been called victims of 'secondary late-onset generalized epilepsy'. They form 16% of a series of 156 epileptic patients who were over 65 years old, and 21% of our own 100 patients.

Two cases of symptomatic common carotid artery occlusion treated by carotid endarterectomy with L-shaped ministernotomy.

Common carotid artery occlusion (CCAO) is rare. Symptomatic lesions are resistant to medical treatment and revascularization are often required, but there is no consensus on the treatment of CCAO. In this paper, two cases of symptomatic CCAO treated by carotid endarterectomy (CEA) with L-shaped ministernotomy, in which the lesions extended to the beginning part of the CCA, are reported. Case 1 involved a 74-year-old man who presented with transient left limb numbness and an abnormal right visual field. Cerebrovascular angiography showed that the right CCA was occluded immediately after its origin and blood was supplied from the posterior circulation. CEA was performed with an L-shaped ministernotomy that allowed exposure of the CCA origin with minimal invasion. There were no complications associated with the sternal incision and he was discharged with a modified Rankin Scale (mRS) score of 0. Case 2 involved a 70-year-old man who presented with left half-blindness. Magnetic resonance imaging showed infarction in the right posterior cerebral artery region and neck echo showed CCA pseudo occlusion just before the carotid bulb. A new infarction in the right middle cerebral artery region developed during hospitalization. CEA with partial sternotomy was performed. The patient was rehabilitated with no deterioration of neurological findings and transferred with an mRS score of 3. There were no complications resulting from partial sternotomy in the two cases presented. CEA with partial sternotomy could be an effective treatment option for CCAO in which the internal carotid artery is patent and thrombus extends to the proximal CCA.

[The problem of early diagnosis of brain tumours causing seizures only (author's transl)].

The diagnosis of brain tumour could not be made in 91 cases at the first investigation in a group of 1155 brain tumours. Slowly growing gliomas causing only epileptic fits and no other symptoms are especially difficult to diagnose. Of 21 personal observations of tumour seizures, in which the diagnosis of the neoplasm was missed at the first investigation in hospital, 9 were oligodendrogliomas, 5 astrocytomas, 3 glioblastomas, 2 spongioblastomas, 1 gangliocytoma and 1 a metastasis. They were all located in the frontal or centroparietal region. In most cases the seizures appeared during the third or fourth decade. The average interval between the first epileptic fit and the tumour diagnosis was 8.2 years in cases of oligodendrogliomas and 2.2 years in astrocytomas. 5 patients had major seizures, 2 had psychomotor attacks and all the others suffered from partial epilepsy. Anticonvulsive therapy was often successfull; either the frequency of the fits diminished or, in 2 cases, the character of the seizures changed. 18 patients had a normal neurostatus at time of the first investigation. Only 3 patients had a slight difference of physiological reflexes, but no other pathological signs. In none of the patients did investigation of the CSF, skull X-rays, brain scanning, pneumencephalography or cerebral angiography first lead to the diagnosis of a brain tumour. The EEG alone showed focal signs corresponding to the location of the tumour in about 50% of the cases.

Surgical treatment for patients with symptomatic generalised seizures due to brain lesions.

To study the role of epilepsy surgery for patients with focal lesions who exhibited the semiology of clinically generalised seizures. From our epilepsy surgery series, we identified 29 patients who underwent surgery for seizures, including certain types of generalised seizures, according to their ictal semiology. We systematically reviewed the brain imaging, video-EEG, surgical operation, and pathological findings data of these patients. All patients had at least one type of generalised seizure according to the semiology; these seizures included epileptic spasms, myoclonic seizures, tonic seizures, atonic seizures and atypical absence seizures. Eight patients had a single type of seizure, 11 patients had two types of seizures, and 10 patients had more than two types of seizures. In addition to symptomatic generalised seizures, complex partial seizures were also recorded in eight patients. In 24 patients, the ictal semiology showed slight asymmetric movements in certain types of seizures. Generalised interictal epileptic discharges were recorded in 24 patients; and generalised ictal epileptic discharges as the only EEG pattern were recorded in 13 patients. Intracranial recording was performed in 20 patients; 10 of whom showed a rhythm of fast activities at the initiation of the seizures. Functional hemispherectomy was performed for three patients with hemispheric lesions. Focal resection of the epileptogenic zone was performed in 26 patients. The resected epileptogenic zones involved a single lobe in 10 patients, two lobes in 11 patients, and three lobes in 5 patients; the parietal lobe was the most commonly involved lobe (in 19 cases). Scar lesions (in 17 patients) were most commonly observed on pathological examination. At the last follow-up (mean 18±8.3 months, range 12-48), 17 (58.6%) patients were seizure-free. Certain patients with local brain lesions can have seizures with specific types of generalised semiology. An appropriate operation may be helpful for a portion of these patients.

Electroclinical and magnetoencephalographic analysis of epilepsy in patients with congenital bilateral perisylvian syndrome.

Epilepsies in four patients with congenital bilateral perisylvian syndrome (CBPS) were studied electroclinically and by magnetoencephalography (MEG) to determine whether cortical dysplasia associated with this syndrome is epileptogenic. We studied three women and one man (mean +/- SD age 30.8 +/- 3.4 years) with a diagnosis of CBPS based on magnetic resonance imaging (MRI). All had drug-resistant epilepsy. In addition to electroclinical analysis, the distribution of equivalent-current dipoles (ECDs) analyzed from MEG signals was examined. Patient 1 had left-sided parietal lobe epilepsy and ECDs clustered in the left temporoparietal lobe. Patient 2 had bilateral, independent temporoparietal lobe epilepsy, and ECDs were found in both hemispheres, with clustering in the right temporoparietal lobe but not in the left hemisphere. Patient 3 presumably had parietal lobe epilepsy with unidentified focus side and ECDs clustered in the left parietal and right temporal lobes. Patient 4 had symptomatic generalized epilepsy, and ECDs were observed in both hemispheres without clustering. In the three patients who had partial epilepsy (patients 1-3), clusters of ECDs overlaid the perisylvian dysplasia and were not found elsewhere. Patients with CBPS may have either symptomatic partial epilepsy or symptomatic generalized epilepsy, and those with partial epilepsy are likely to have temporoparietal foci. In addition, cortical dysplasia is closely related to the generation of partial seizures and may be epileptogenic per se. However, this study did not elucidate the relationship between cortical dysplasia and CBPS-generated generalized epilepsy.

[Periodic lateralized epileptiform discharges. I. Clinical and electroencephalographic aspects].

In a two-years period, from a total of 5481 EEGs, we could select 25, corresponding to 22 patients, with PLEDs (prevalence of 0.45%). The group was composed by 13 males and 9 females, with age ranging from 5 months to 85 years. Main diagnosis was epilepsy of unknown etiology and brain tumor (22% each). The localization of PLEDs was mainly temporal region (54% of the whole group) and more frequent morphology was "delta triphasic wave" (a graphic pattern resembling sharp wave, but with longer duration) (1/3 of total), followed by sharp biphasic wave and sharp wave-slow wave (29% each). Although 9 patients died it was not possible to determine prognostic value of PLEDs specifically for each pathological condition.

Effects of zonisamide monotherapy in children with epilepsy.

This study examined the efficacy and safety of zonisamide as monotherapy in pediatric patients with epilepsy. Seventy-seven children with epilepsy (ages 8 months-15 years) were treated with zonisamide. Nine patients were withdrawn early because of side effects; these patients were included in side effect but not efficacy analyses. Zonisamide dosages were initiated at approximately 2 mg/kg per day and adjusted for each patient individually to a maximum of 12 mg/kg per day. Among 44 patients with cryptogenic/symptomatic partial epilepsy, 36 (82%) became seizure free; 4 (9%) had a > or =50% reduction in seizure frequency; and 4 (9%) had no change in seizures with zonisamide treatment. Of 11 patients with cryptogenic/symptomatic generalized epilepsy, 10 (91%) became seizure free, and 1 experienced no change with zonisamide treatment. Similarly, 4 patients (100%) with idiopathic partial epilepsy, and 8 of 9 patients (89%) with idiopathic generalized epilepsy became seizure free with zonisamide treatment; in the last group, 1 experienced no change. Thirty patients (39%) reported side effects, including somnolence (11.7%), decreased spontaneity (7.8%), anorexia (6.5%), and rash (6.5%). Thus, zonisamide is effective for partial seizures with or without secondarily generalized seizures in children and should be considered a broad-spectrum antiepilepsy agent.

Classification of partial epilepsies according to the symptomatology of seizures: practical value and prognostic implications.

Among 1,000 outpatient epileptics who visited the Epilepsy Center of Bologna consecutively from 1974 to 1978, 596 cases of partial epilepsy (PE) were chosen, representing 62.9% of all cases classified according to the International Classification of epilepsies. Fifty-four of these cases (5.7%) of those classifiable) that were affected by benign infantile epilepsy with rolandic spikes were not analyzed further. The remaining cases were divided up into three groups based on the symptomatology of the seizures: (1) partial elementary epilepsy (PEE), 102 cases (10.8%); (2) partial complex epilepsy (PCE), 332 cases (35%); and (3) partial secondarily generalized epilepsy (PSGE), 108 cases (11.4%). The three groups were compared according to the parameters that distinguish recognized epileptic syndromes, in order to see whether they constitute autonomous nosographic entities. Among the three groups, significant differences did not arise with regard to the incidence of single lesional etiological factors, the age of onset of the epilepsy, the neurological context, and the general features of interictal EEG. PSGE instead differs significantly from the other two forms for the minor severity of the epilepsy at first examination and for its more favorable course: after at least 2 years of follow-up under treatment, the epilepsy appeared to be controlled in 60.6% of the cases with PSGE, in 31.6% of those with PEE, and in 37.5% of those with PCE (p less than 0.05). For those with PE, globally considered, only three parameters have a favorable prognostic value: the brief duration of the epilepsy at the first observation, the rarity of the seizures, and the presence of only one type of seizure.

Epilepsy syndromes

Febrile infection-related epilepsy syndrome Febrile infection-related epilepsy syndrome (FIRES) Frontal lobe epilepsy Frontal lobe epilepsy, usually a symptomatic or cryptogenic localization-related epilepsy, arises from lesions causing seizures that occur in the frontal lobes of the brain. These epilepsies can be difficult to diagnose because the symptoms of seizures can easily be confused with nonepileptic spells and, because of limitations of the EEG, be difficult to "see" with standard scalp EEG. Juvenile absence epilepsy is an idiopathic generalized epilepsy with later onset than CAE, typically in prepubertal adolescence, with the most frequent seizure type being absence seizures. Generalized tonic-clonic seizures can occur. Often, 3 Hz spike-wave or multiple spike discharges can be seen on EEG. The prognosis is mixed, with some patients going on to a syndrome that is poorly distinguishable from JME.

Asymmetric ending of secondarily generalized seizures: a lateralizing sign in TLE.

The authors investigated whether asymmetric ending of the clonic phase of secondarily generalized tonic clonic seizures (SGTCS) has lateralizing value concerning the hemisphere of seizure onset. They studied 70 patients with mesial temporal lobe epilepsy who underwent epilepsy surgery. Asymmetric ending of the clonic phase occurred in 43% of patients. The last clonic movement appeared on the upper extremity ipsilateral to the hemisphere of seizure onset in 83%.

Cryptogenic partial epilepsies with anti-GM1 antibodies: a new form of immune-mediated epilepsy?

We wished to study immune system dysfunction which has been proposed as a potential cause of epilepsy. Epileptogenic action of antibodies directed against GM1 gangliosides was demonstrated in rats, but the potential role of anti-GM1 antibodies in human epilepsy has not yet been studied. We investigated the presence of IgG or IgM anti-GM1 antibodies in the sera of 64 patients with various types of epileptic syndromes: idiopathic generalized epilepsy (IGE) (n = 6), symptomatic or cryptogenic generalized epilepsy (SCGE) (n = 7), symptomatic partial epilepsy (SPE) (n = 26), and cryptogenic partial epilepsy (CPE) (n = 25). Two patients had elevated titers of IgM anti-GM1 antibodies, one patient had elevated titers of both IgM and IgG anti-GM1 antibodies, and 1 patient had elevated titers of IgG anti-GM1 antibodies. All 4 patients had complex partial seizures (CPS) secondarily generalized, drug resistance, psychiatric disorders, and normal brain imaging. Anti-GM1 antibodies were never associated with IGE, SCGE, or SPE. We compared the reactivity of sera from these patients with the sera from 5 patients with motor neuropathies with conduction block (MNCB) against different gangliosides and concluded that epilepsy sera did not react with the Gal(beta 1-3)GalNAc epitope. Two anti-GM1-positive patients were treated successfully with high-dose intravenous immunoglobulins (IgIV). Our findings suggest that detection of anti-GM1 antibodies could allow identification of a subgroup of patients with partial epilepsy associated with an autoimmune response. If anti-GM1 antibodies prove pathogenic, they could be an important prognostic factor for drug resistance and worsening of seizures.

Frontal lobe epilepsy: clinical characteristics, surgical outcomes and diagnostic modalities.

To identify surgical prognostic factors and to characterize clinical features according to the location of the intracranial ictal onset zone of frontal lobe epilepsy (FLE) in order to assess the role of various diagnostic modalities, including concordances with presurgical evaluations. We studied 71 FLE patients who underwent epilepsy surgery and whose outcomes were followed for more than 2 years. Diagnoses were established by standard presurgical evaluation. Clinical manifestations could be categorized into six types: initial focal motor (9 patients), initial versive seizure (15), frontal lobe complex partial seizure (14), complex partial seizure mimicking temporal lobe epilepsy (18), initial tonic elevation of arms (11), and sudden secondary generalized tonic-clonic seizure (4). Thirty-seven patients became seizure-free after surgery. Five patients were deleted in the analysis because of incomplete resection of ictal onset zones. The positive predictive value of interictal EEG, ictal EEG, MRI, PET, and ictal SPECT, respectively were 62.5%, 56.4%, 73.9%, 63.2%, and 63.6%, and the negative predictive value were 46.0%, 44.4%, 53.5%, 44.7%, and 51.7%. No significant relationship was found between the diagnostic accuracy of these modalities and surgical outcome, with the exception of MRI (p=0.029). Significant concordance of two or more modalities was observed in patients who became seizure-free (p=0.011). We could not find any clinical characteristic related to surgical outcome besides seizure frequency. No definite relationship was found between the location of intracranial ictal onset zone and clinical semiology. Although various diagnostic methods can be useful in the diagnosis of FLE, only MRI can predict surgical outcome. Concordance between presurgical evaluations indicates a better surgical outcome.

[When and how should the long-term anti-epileptic treatment be stopped].

Although for some decades it has been customary to stop long-term treatment of epilepsy in patients who have been free of crises for several years, there is still no general agreement as to when, how and in which cases such treatment should be stopped. Several factors have to be taken into account when making such a decision: the known toxicity of anti-epileptic drugs; the fact that 10-20% of the patients on such treatment have recurrences of their epileptic crises and that around 25% of the children and 40% of the adults relapse when long-term treatment is stopped. On the other hand, factors which reduce the risk of relapse have recently been identified. When the psychological benefit of no longer having to take anti-epileptic drugs together with their high cost are also considered, it would seem advisable to stop treatment when the patient has had no epileptic crises for several years. Since there is no significant difference in the frequency of relapses when anti-epileptic drugs are suspended 2-5 years after the last crises, and these crises are more frequent when paroxystic activity is seen on the EEG before stopping the drugs, we recommend that treatment be stopped after 2 years free of crises in idiopathic epilepsy, after 3 years with no sign of abnormality in the EEG in patients with partial cryptogenic epilepsy and after at least 4 years without crises and 2 years of normal EEG in patients with partial symptomatic or generalized cryptogenic or symptomatic epilepsy. The criteria for suspending drug treatment should take account of the pharmacokinetic features and permit EEG control. Therefore we recommend that 40% of the total dose be stopped during the first 6 months at a rate of 20% every three months and then a further 20% every two months until medication has been stopped completely.

[Errors in the differential diagnosis of different types of nonepileptic paroxysms in the initial period of their occurrence].

As many as 635 patients were referred to the Antiepileptic Center for counselling and examination. They had been diagnosed to suffer from epilepsy or the epileptic syndrome within the period from several days to 3 years since the moment of the first paroxysms. In 70 patients, the epileptic nature of the paroxysms was not confirmed, i. e. the primary diagnosis turned out to be erroneous. The paroxysms estimated at first as epileptic were systematized. The basis was formed by vegetative or vegetative visceral paroxysms of different character and gravity, which went, in the majority of cases, with loss of consciousness and, in rare cases, with unmarked convulsive component. 10 patients subjected to the EEG manifested fairly moderate epileptiform alterations and only one patient demonstrated paroxysmal diffuse epileptic activity. The author provides a number of clinical differential diagnostic criteria for the nonepileptic paroxysmal states that occurred for the first time. It is indicated that the EEG, the biochemical and other paraclinical methods of the diagnosis made in the initial disease stage may turn out abortive.


The correct answer is: 3. Subcutaneous fat biopsy. Lupus erythematosus, some vasculitides, Goodpasture's disease and other systemic diseases (ankylosing spondylitis is one of them) affect the kidney and condition its prognosis. The appearance of urinary abnormalities or renal impairment of parenchymal cause are indications for renal biopsy, even with proteinuria ranges lower than those accepted in primary nephropathies. The determination of anti-GBM antibodies and ANCAS are helpful for diagnosis, but they do not replace renal biopsy, since they lack prognostic value and do not help to plan treatment. In this case, in which we are led to think that renal biopsy is not possible, we must relate AE to renal failure. In most cases, the relationship is established by an IgA nephropathy, which presents with hematuria, a symptom that claims not to exist in this case. A non-negligible number of patients with evolved AD is amyloidosis, which also matches the patient's symptomatology. Therefore, and given that amyloidosis can be diagnosed with a subcutaneous fat biopsy, it is answer 3 that should be considered valid.

[HIDDEN] Lupus erythematosus, some vasculitides, Goodpasture's disease and other systemic diseases (ankylosing spondylitis is one of them) affect the kidney and condition its prognosis. The appearance of urinary abnormalities or renal impairment of parenchymal cause are indications for renal biopsy, even with proteinuria ranges lower than those accepted in primary nephropathies. The determination of anti-GBM antibodies and ANCAS are helpful for diagnosis, but they do not replace renal biopsy, since they lack prognostic value and do not help to plan treatment. In this case, in which we are led to think that renal biopsy is not possible, we must relate AE to renal failure. In most cases, the relationship is established by an IgA nephropathy, which presents with hematuria, a symptom that claims not to exist in this case. A non-negligible number of patients with evolved AD is amyloidosis, which also matches the patient's symptomatology. Therefore, and given that amyloidosis can be diagnosed with a subcutaneous fat biopsy, it is answer [HIDDEN] that should be considered valid.

A 66-year-old man with a history of ankylosing spondylitis of long evolution. He presents proteinuria of 6 grams per day with hypoalbuminemia and edema. In the urinary sediment no hematuria is detected. His plasma creatinine is 1.6 mg/dL and his glomerular filtration rate is 45 mL/min. Glycemia 110 mg/dL. His severe spinal deformity makes it difficult to perform percutaneous renal biopsy. What is the correct initial approach?

To initiate corticoids for suspicion of minimal change glomerular disease.

Treat with cyclophosphamide for suspected membranous glomerulopathy.

Glucose overload test to rule out diabetic nephropathy.

Glomerular filtration rate

A urinalysis is helpful even when not showing any pathology, as this finding suggests an extrarenal etiology. Proteinuria and/or urinary sediment usually indicates the presence of glomerular disease. Hematuria may be caused by glomerular disease or by a disease along the urinary tract. The most relevant assessments in a renal ultrasound are renal sizes, echogenicity and any signs of hydronephrosis. Renal enlargement usually indicates diabetic nephropathy, focal segmental glomerular sclerosis or myeloma. Renal atrophy suggests longstanding chronic renal disease. Chronic kidney disease stages

Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Diabetic nephropathy

It is recommended that diabetics have their albumin levels checked annually, beginning immediately after a diagnosis of type 2 diabetes and five years after a diagnosis of type 1 diabetes. Medical imaging of the kidneys, generally by ultrasonography, is recommended as part of a differential diagnosis if there is suspicion of urinary tract obstruction, urinary tract infection, kidney stones or polycystic kidney disease. Conformation kidney biopsy should only be performed if non-diabetic kidney disease is suspected. Urine analysis in patients with diabetic kidney disease is often bland. In cases of severely increased microalbuminuria, hematuria might be present. fat bodies might be present in patients who develop nephrotic-range proteinuria. Staging To stage the degree of damage in this (and any) kidney disease, the serum creatinine is determined and used to calculate the estimated glomerular filtration rate (eGFR). Normal eGFR is equal to or greater than 90ml/min/1.73 m2.

[Case of mesangial proliferative glomerulonephritis complicated with multicentric Castleman's disease].

We report a case of a 47-year-old man with multicentric Castleman's disease (MCD) and progressive renal dysfunction due to mesangial proliferative glomerulonephritis, possibly from IgA nephropathy. At age 36 years, he was referred to a hematologist due to hypergammaglobulinemia. Because of systemic lymph node swelling, he underwent right cervical lymph node biopsy at age 41 years and MCD (plasma cell type)was diagnosed. During this period, microscopic hematuria and persistent proteinuria occurred and his renal function deteriorated (serum creatinine (Cr) rising from 0.7 mg/dL to 1.4 mg/dL). Treatment with intravenous methylprednisolone at the dose of 1 g daily for 3 days followed by oral prednisolone at 20 mg daily reduced his lymphadenopathy and improved the renal function. However, his renal function deteriorated again, from Cr 0.8 mg/dL to 1.8 mg/dL over 6 years in line with gradual prednisolone tapering to 6 mg daily. At age 47 years, he was referred to our nephrology department and underwent a renal biopsy. The microscopic examination showed IgA nephropathy with crescent formation, accompanied by mild lymphoplasmacytic tubulointerstitial nephritis. Treatment with the same dose of intravenous methylprednisolone therapy followed by oral prednisolone at 40 mg daily, improved his proteinuria, hematuria and renal dysfunction. The coexistence of MCD and IgA nephropathy is a rare phenomenon. In addition, IL-6, overproduced by MCD might have influenced the mesangial cell proliferation and the activity of IgA nephropathy in the present case.

[Importance of the duration from the onset of a urinary abnormality until a biopsy is performed: a multivariate analysis on the application of renal biopsy for patients with IgA nephropathy].

To clarify the importance of the duration from the onset of a urinary abnormality until a biopsy is actually performed (UA-Bx time) in making a renal prognosis, we investigated 496 patients with IgA nephropathy (male/female: 222/274, mean age: 33.0 +/- 13.7 yrs, mean follow-up period: 10.8 +/- 4.3 yrs). All patients were found to have a urinary abnormality, including both hematuria and proteinuria, at clinical onset while demonstrating a normal renal function, and showing a serum creatinine level of < or = 1.2 mg/dl or a creatinine clearance level of > or = 80 ml/min. The UA-Bx time was divided into 3 groups: < 1 yrs (S-G), 1 < or = < 3 yrs (M-G), > or = 3 yrs (L-G). The severity of glomerular damage was divided into 5 groups based on the occupational rate of segmental sclerotic glomeruli. Based on a multivariate analysis of independent prognostic factors relating to renal death, the severity of glomerular damage was the most independent factor, while the UA-Bx time showed no risk for renal death. However, based on a multivariate analysis of the UA-Bx time regarding the timing of a renal biopsy, patients in L-G, which had the most glomerular damage, showed twice the hazard ratio as those in S-G or M-G and the difference was significant. These results thus indicate that because the glomerular damage is able to progress for 3 yrs or longer after the clinical onset of renal disease, a renal biopsy should therefore be performed within 3 yrs from the clinical onset in patients demonstrating both hematuria and proteinuria when such patients are also suspected of having IgA nephropathy.

InternalMed_Harrison

The natural history of diabetic nephropathy is characterized by a fairly predictable sequence of events that was initially defined for individuals with type 1 DM but appears to be similar in type 2 DM (Fig. 419-3). Glomerular hyperperfusion and renal hypertrophy occur in the first years after the onset of DM and are associated with an increase of the glomerular filtration rate (GFR). During the first 5 years of DM, thickening of the glomerular basement membrane, glomerular hypertrophy, and mesangial volume expansion occur as the GFR returns to normal. After 5–10 years of type 1 DM, many individuals begin to excrete small amounts of albumin in the urine. The American Diabetes Association (ADA) recently suggested that the terms previously used to refer to increased urinary protein (microalbuminuria as defined as 30–299 mg/d in a 24-h collection or 30–299 μg/mg creatinine in a spot collection or macroalbuminuria as defined as >300 mg/24 h) be replaced by the phrases “persistent

Nephrotic syndrome

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m2 per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance CCr test will evaluate kidney function particularly the glomerular filtration capacity. Creatinine formation is a result of

[Instructions and implementations for percutaneous renal biopsy. Guidelines for the therapy of glomerular nephropaties].

This series of articles on the management of glomerulonephritis (GN) has been prepared by a team of experts in the evidence-based format consistent with peer review of published data. Each author was asked to review the literature for his assigned histological type, with emphasis on therapy and limited to adult studies. The age limit was not considered for minimal change disease and focal segmental glomerulosclerosis, because of the high prevalence of these glomerulopathies in children. The particular treatment recommendations for each type of glomerular disease were graded by each author according to the amount of evidence provided in these reviewed studies. The first two articles concentrate on indications and techniques for kidney biopsy. Each subsequent article focuses on and describes the highest level of evidence supporting the recommendation for therapy in IgA nephropathy (Ig-GN), minimal change nephropathy (MCN) and focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis, ANCA-associated vasculitis, HCV-associated cryoglobulinaemia and renal involvement in paraproteinemic disorders. The article on IgA nephropathy emphasises the importance of carefully evaluating both clinical and histologic findings before settling on the treatment. The recent, renewed interest in steroids and many immunosuppressive agents is discussed in detail. Recommendations related to the patient's age are also provided. MCN and FSGS are treated together because these forms share similar evidence-based recommendations. For both of these diseases, in fact, the initial treatment approach in children should be prednisone or prednisolone for four to six weeks. The therapeutic response in adults is slower than in children, but adults experience fewer relapses and a more prolonged remission. There is also a discussion on treatment of relapse, frequent relapsing disease and true steroid-resistant disease as well as the role of new immunosuppressive agents. Membranous nephropathy is a frequent cause of nephrotic syndrome in adults and, in one third of these patients, leads to end-stage renal disease. However, the treatment of this form is as yet a matter of discussion. Based on extensive critical review of the literature, the following recommendations are put forward: (a) no treatment in the absence of nephrotic syndrome; (b) patients with heavy proteinuria should receive a 6-month treatment with i.v. methylprednisolone (MP) pulse therapy for three consecutive days followed by oral MP (0.4 mg/kg/day) (months 1, 3, 5) and chlorambucil or cyclophosphamide (months 2, 4, 6); (c) the dosage of chlorambucil or cyclophosphamide should be lowered in older patients; (d) cyclosporine is a second-choice treatment. The treatment of lupus nephritis depends on the histologic class. No specific treatment is usually necessary for class I and IIA. Oral steroids are indicated in patients with class IIb, proteinuria and active systemic disease. Steroids and azathioprine are the treatment of choice for patients with class III and IV, but cyclosporine can be an effective alternative therapy. Cyclophosphamide is more effective than azathioprine when severe acute renal involvement is present. The treatment of ANCA-associated vasculitis depends mainly on clinical presentation, oral prednisone + oral or i.v. cyclophosphamide are generally effective. In the most severe cases, the association of MP pulse therapy with cyclophosphamide is probably more effective. Plasma exchange is probably justified in unresponsive patients. Azathioprine should replace cyclophosphamide during the maintenance therapy. In HCV-associated mixed cryoglobulinemia the treatment also depends on the severity of renal involvement. The treatment for chronic HCV infection involves alpha interferon alone or preferably in combination with ribavirin. Aggressive therapy, including i.v. MP, plasmapheresis and cyclophosphamide is primarily reserved for patients with acute severe disease, as manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy. Uncontrolled studies suggest that this regimen can improve renal function. Renal involvement is a common problem in paraproteinemic disorders that include multiple myeloma, Waldentrom's macroglobulinaemia and monoclonal gammopathy. The most common renal diseases in this setting are cast nephropathy, primary amyloidosis cast nephropathy, primary amyloidosis, and light chain deposition disease that are related to the overproduction of monoclonal immunoglobulin light chains. The approach to therapy varies with the cause of the renal dysfunction. Patients with amyloidosis or light-chain deposition disease are generally treated with chemotherapy, but the most effective therapy for myeloma kidney is prevention by minimising the risk factors that promote light chain filtration and subsequent obstruction by cast formation within the tubules. Chemotherapy or stem cell or bone marrow transplantation to decrease filtered light chain load, prevent volume depletion and maintain high fluid intake to reduce light chain concentration within the tubular lumen are indicated in almost all the patients.

An attempt to extend the donor criteria for successful living-related kidney transplantation from a donor with membranous nephropathy.

Marginally appropriate donors may be considered to extend the donor criteria for renal transplantation because of the donor shortage. We have reported a successful outcome after kidney transplantation from a living-related donor diagnosed with membranous nephropathy. A 38-year-old man began continuous ambulatory peritoneal dialysis (CAPD) at the age of 37. His 63-year-old father showed mild proteinuria, diagnosed as membranous nephropathy by needle biopsy. However, the father had normal renal function on preoperative examination, except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father who was diagnosed with membranous nephropathy into his son using a cyclosporine (CsA)-based immunosuppressive regimen. The postoperative course was good in both the recipient and the donor without rejection or infection. At 57 months after transplantation, the serum creatinine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. An allograft needle biopsy at 39 months after transplantation showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Electron microscopy showed decreased electron-dense deposits and electron-lucent washout lesions with thickening of the GBM. This was diagnosed as stage IV membranous nephropathy, resulting from clearance of immune complexes and histological repair of the GBM. For the present donor, graft donation did not affect his residual renal function. Preexisting membranous nephropathy itself may show remission after transplantation into the recipient to achieve successful results, however, long-term careful observation of both the donor and recipient is required.

InternalMed_Harrison

The natural history of diabetic nephropathy in patients with types 1 and 2 diabetes is similar. However, since the onset of type 1 diabetes is readily identifiable and the onset of type 2 diabetes is not, a patient newly diagnosed with type 2 diabetes may present with advanced diabetic nephropathy. At the onset of diabetes, renal hypertrophy and glomerular hyperfiltration are present. The degree of glomerular hyperfiltration correlates with the subsequent risk of clinically significant nephropathy. In the approximately 40% of patients with diabetes who develop diabetic nephropathy, the earliest manifestation is an increase in albuminuria detected by sensitive radioimmunoassay (Table 338-1). Albuminuria in the range of 30–300 mg/24 h is called microalbuminuria. Microalbuminuria appears 5–10 years after the onset of diabetes. It is currently recommended to test patients with type 1 disease for microalbuminuria 5 years after diagnosis of diabetes and yearly thereafter and, because the

InternalMed_Harrison

PROTEINURIA ON URINE DIPSTICK Quantify by 24-h urinary excretion of protein and albumin or first morning spot albumin-to-creatinine ratio RBCs or RBC casts on urinalysis In addition to disorders listed under microalbuminuria consider Myeloma-associated kidney disease (check UPEP) Intermittent proteinuria Postural proteinuria Congestive heart failure Fever Exercise Go to Fig. 61-2 Macroalbuminuria 300-3500 mg/d or 300-3500 mg/g Microalbuminuria 30-300 mg/d or 30-300 mg/g Nephrotic range > 3500 mg/d or > 3500 mg/g + Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts)Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts) Nephrotic syndrome Diabetes Amyloidosis Minimal change disease FSGS Membranous glomerulopathy IgA nephropathy

Assessment of kidney function

Kidney function in disease A decreased renal function can be caused by many types of kidney disease. Upon presentation of decreased renal function, it is recommended to perform a history and physical examination, as well as performing a renal ultrasound and a urinalysis. The most relevant items in the history are medications, edema, nocturia, gross hematuria, family history of kidney disease, diabetes and polyuria. The most important items in a physical examination are signs of vasculitis, lupus erythematosus, diabetes, endocarditis and hypertension. A urinalysis is helpful even when not showing any pathology, as this finding suggests an extrarenal etiology. Proteinuria and/or urinary sediment usually indicates the presence of glomerular disease. Hematuria may be caused by glomerular disease or by a disease along the urinary tract.

[The classics of Italian nephrology: the monograph "La nefropatia diabetica" (Diabetic nephropathy) by Luigi Scapellato (1918-1998)].

This monograph, published in 1953, describes the findings observed by the author in a cohort of patients affected by diabetes mellitus and renal disease. From a pathological standpoint, the typical renal lesion is represented by ''nodular intercapillary glomerulosclerosis'', which is present in 8 out of 20 patients at postmortem. Marked proteinuria and edema are the most typical clinical features. Urinary sediment examination is the only test allowing to differentiate diabetic nephropathy from other glomerular diseases. In the initial phases, the glomerular filtration rate is increased rather than reduced. The evolution is almost invariably towards end-stage renal disease, and a hypoglucidic diet and insulin are the only therapeutic modalities available. Today this work shows us, on the one hand, how many uncertainties still existed about diabetic nephropathy 17 years after its first description by Kimmelstiel and Wilson in 1936. On the other hand, it shows how much relevant and still valid information was already known at the time. Luigi Scapellato, who is almost completely forgotten today, began his career at the Clinica Medica of the University of Rome under the guidance of Cesare Frugoni (1881-1978). In 1959, he moved to Syracuse (Sicily) to work as director of the internal medicine unit of the ''Umberto I'' Hospital. In April 1957 he was among the 13 founders of the Italian Society of Nephrology.

A case report of remission of refractory membranous nephropathy progressing to stage 4 chronic kidney disease using low-dose rituximab: A long-term follow-up.

As suggested by the 2012 KDIGO guidelines, persistent elevation of serum creatinine > 3.5 mg/dl (> 309 μmol/l) (or an estimated glomerular filtration rate < 30 ml/min per 1.73 m is one of contradictions for the use of immunosuppressive therapy in membranous nephropathy. A 45-year-old man with membranous nephropathy negative for serum anti-phospholipase-A2-receptor antibody, showed no response to corticosteroids and cyclophosphamide. He progressed to chronic kidney disease stage 4 (CKD4) under tacrolimus and relapsed after withdrawal. The patient received repeated renal biopsy, comfirming the diagnosis of membranous nephropathy with progressive glomerular and tubulointerstitial scarring. He was treated with successfully four times with lose-dose (180 mg/m every 2-3 months) rituximab (RTX) depending on his B cell counts, aiming to remain at 0-5 cells/μl. The patient was followed-up for almost 6 years. He achieved a partial remission at 11 months and a complete remission of the nephritic range of proteinuria at 34 months following infusion of RTX. RTX was well tolerated and the patient's renal function improved. He had no edema and his dosage of corticosteroids could be discontinued. This case strongly suggested that rituximab has promising therapeutic significance, even in patients progressing to CKD4.

[Prognostic significance of persistent massive proteinuria in progressive IgA nephropathy--a long-term follow-up study].

The most reliable factors predicting a long-term prognosis in individual progressive IgA nephropathy patients were evaluated. Ninety-eight cases who showed moderate to severe histological alterations (total score of 7 or more) and were continuously followed up for 10 years or more from the first biopsy were the subjects of this study. During the follow-up period of 10 years, 52 of the 98 cases went into hemodialysis treatment (HD). All 24 cases who had a higher total score of 17 or more, or severe renal dysfunction of less than 60 ml/min in their initial Ccr values went into HD. The remaining 74 cases who showed both a total score below 16 and initial Ccr values of 60 ml/min or more were divided into two groups in their clinical courses: 28 (group I) of the 74 cases went into HD and the other 46 (group II) did not. The degree of initial proteinuria was significantly different between groups I and II, but the degree of individual proteinuria was in a similar range from 0.5 to 2.5 g/day in most cases of both groups. Therefore, in order to clarify a more precise factor associated with the individual prognosis, the % duration of massive proteinuria (% DP) was calculated in individual cases. The % DP was more significantly different between groups I and II (82.6 +/- 26.1 vs 19.6 +/- 27.3%, p < 0.01). Moreover, all cases but one in group I showed 30% or more in % DP and 35 of 46 cases in group II showed 30% or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast-induced nephropathy

Roxana Mehran score The Roxana Mehran score is a clinical prediction rule to estimate probability of nephropathy (increase ≥25% and/or ≥0.5 mg/dl in serum creatinine at 48 h): Risk Factors: Systolic blood pressure <80 mm Hg - 5 points (if systolic BP less than 80 mmHg for at least one hour requiring inotropic support) Intra-arterial balloon pump - 5 points Congestive heart failure, counting as NYHA class III (marked limitation in activity due to symptoms, even during less-than-ordinary activity) or worse, or history of pulmonary edema - 5 points Age >75 y - 4 points Hematocrit level <39% for men and <35% for women - 3 points Diabetes mellitus- 3 points Contrast media volume - 1 point for each 100 mL Decreased kidney function: Serum creatinine level >1.5 g/dL - 4 points or Estimated Glomerular filtration rate (online calculator) 2 for 40–60 mL/min/1.73 m2 4 for 20–40 mL/min/1.73 m2 6 for < 20 mL/min/1.73 m2

[For or against renal biopsy after 65 years].

Kidney biopsy (KB) is controversial in the elderly because it is generally felt that the risks exceed the potential therapeutic benefits. In this review of our personal experience and the literature reports, we discuss the risks of this diagnostic procedure and its use in the four main circumstances of patient referral. On the one hand, KB does not seem to be more hazardous in the elderly, provided that it is not performed in patients in poor condition or with atrophic kidneys or suspected vascular lesions. On the other hand, KB is clearly useful in a number of elderly patients either to assess the diagnosis of a systemic disease involving the kidney or to select the appropriate treatment. 1. In patients with non nephrotic proteinuria, KB should be performed if the proteinuria is associated with extra-renal signs suggestive of systemic disease or with deterioration of renal function. 2. Nephrotic syndrome without evidence of amyloidosis and diabetes, should lead to KB to identify patients with minimal change disease (MCD) requiring steroid treatment. Indeed, MCD can rarely be suspected on clinical grounds as the resulting nephrotic syndrome is rarely "pure" at this age. 3. In acute renal failure, KB seems to be essential and urgent in patients with rapidly progressive glomerulonephritis and in those with renal failure of dubious origin to select the most appropriate treatment according to the etiology and the type of renal lesions (sclerotic or "active"). 4. KB is useless and hazardous in chronic renal failure, except in case of unexplained rapid worsening of renal function in patients with previously moderate renal failure.

Behcet's disease and IgA nephropathy: report of this association in a patient from Brazil and literature review.

Behcet's disease (BD) is associated with renal involvement in about one-third of the cases and a variety of renal lesions have been reported. A 27-year-old man presented a history of recurrent oral and genital ulcers, associated with pseudofoliculitis and arthritis in his left knee. The first laboratory tests revealed: urea = 53mg/dL, creatinine = 1.8 mg/dL. The urinalysis showed leukocyturia. Initial treatment with ceftriaxone, thalidomide and prednisone was instituted. He became clinically stable, with normal renal function, but presenting hematuria and proteinuria. One year later the patient presented dark urine. The new laboratory tests showed urea=58 mg/dL, creatinine = 1.4 mg/dL, and mild proteinuria (500-1000 mg/24h). Two years later the proteinuria was 2230 mg/day. The renal biopsy showed one glomerulus with severe glomerular sclerosis, mild tubular atrophy, mild interstitial fibrosis and thickening of arterial walls. Treatment with captopril was started to decrease proteinuria. Two years later, the patient presented creatinine = 1.7 mg/dL and proteinuria = 2509 mg/day. A new renal biopsy evidenced proliferative crescentic glomerulonephritis, with diffuse granullary deposits of IgA, IgM and C3. It was instituted pulsotherapy with metilprednisolone, monthly endovenous cyclophosphamide and maintenance prednisone. The patient became clinically stable, with creatinine of 1.3 mg/dL and proteinuria of 500 mg/day. BD could be one of the various causes of secondary IgA nephritis. It is important to periodically perform renal function evaluation in patients with BD, through urinalysis and measurement of serum creatinine and its clearance, in order to detect any abnormality and provide an early adequate treatment.

Rapidly progressive glomerulonephritis superimposed on diabetic glomerulosclerosis. Recognition and treatment.

Two patients with long-standing diabetes mellitus and diabetic retinopathy were evaluated for declining renal function and heavy albuminuria. Initially, diabetic glomerulosclerosis was suspected as the cause of progressive glomerulopathy. However, in both patients the rate of loss of glomerular filtration rate was greater than that usually seen in diabetic glomerulosclerosis, and the urine sediment contained many RBC casts. These findings led to renal biopsy, which demonstrated crescentic glomerulonephritis superimposed on diabetic glomerulopathy. Both patients were treated with prednisone and cyclophosphamide and both experienced substantial improvement in renal function. These experiences demonstrate the importance of searching for evidence of a superimposed treatable glomerulopathy in the diabetic patient with glomerulopathy and advancing renal insufficiency.

Glomerulonephrosis

Due to its close connection with other diseases and disorders, glomerulonephrosis is rarely diagnosed independently and is superseded by those other conditions. The primary test to diagnose a form of glomerulonephrosis is a urinalysis to look for any proteinuria. This is a very important step as an otherwise healthy individual will have low protein levels in the urine. A Comprehensive metabolic panel (CMP) is also often used to test for hypoalbuminemia, levels of albumin lower than ≤2.5 g/dL. This is a key step in differentiating glomerulonephrosis from conditions that also cause proteinuria, such as multiple myeloma and diabetes mellitus, that are not marked by hypoalbuminemia. A Creatinine ClearanceCR test will also be used to determine the glomerular filtration rate (GFR), or the rate at which blood flows through the glomerulus. Creatinine is a byproduct of creatine metabolism that will be released as waste in urine, so it is a good benchmark for estimating how much fluid is being

Recurrent proteinuria with graft dysfunction: a diagnostic and clinical conundrum.

The index case is a 45-year old male with unknown cause for native kidney disease, who received a kidney from his wife. Antithymocyte globulin (ATG) was used for induction, and tacrolimus, mycophenolate mofetil and prednisolone were prescribed for maintenance. His baseline serum creatinine was 0.9 mg/dl. Two years after the transplant, the patient developed 3+ proteinuria on routine urinalysis with stable graft function. His 24-hour urinary protein was 2.3 grams, serum albumin was 3.0 g/dl, and the total cholesterol was 251 mg/dl. The tacrolimus C0 levels were maintained between 6 and 8 ng/ml range. Allograft biopsy revealed diffuse thickening of glomerular basement membranes, with the immunofluorescence showing 2+ granular positivity along the loops for IgG and C3. Further, tissue staining for PLA2R and THD7A were both negative. Also, no donor-specific antibodies (DSA) were detected, and serum PLA2R antibody assay was also negative. The patient was managed conservatively with losartan 50 mg and atorvastatin 20 mg, with subsequent reports of proteinuria of 1.5-2.0 grams/day. After 52 months of renal transplant, the patient presented with a serum creatinine of 2.06 mg/dl and proteinuria of 6.8 grams/day. A repeat allograft biopsy revealed thickened glomerular basement membranes with spikes on silver staining. (Figure 1a) Further, immunofluorescence studies showed 2+-3+ granular positivity for IgG, C3, with the added findings of C4d positivity on the peritubular capillaries and tissue PLA2R positivity on the basement membranes by immunohistochemistry. (Figures 1b-d) The biopsy also revealed peritubular capillaritis and acute tubular injury. Antibodies to donor Class II (HLA DR) were positive with a mean fluorescence intensity (MFI) of 6885, but serum PLA2R antibodies remained negative. Based on these findings, the patient was treated with pulse methylprednisolone, 5 sessions of plasma exchange at 40 ml/kg with 5% human albumin and fresh frozen plasma replacement, intravenous immunoglobulin (at 100 mg/kg × 5) and rituximab (two doses of 1 g 2 weeks apart). Subsequently, the serum creatinine settled to 1.6 mg/dl, and DSA reduced to < 500 MFI. Three months after discharge, the serum creatinine is 1.5 mg/dl, 24-hour urine protein is 982 mg/day and follow-up DSA remains negative.

[Steroid-responsive nephrotic syndrome in IgA nephropathy].

A 46-year-old male, smoker of half a packet a day and an alcohol intake of 80 grams a day, with an unremarkable medical history, was referred to our service in the year 1988 for a study of nephrotic syndrome. He presented normal renal function, without either microhematuria nor hypertension. In blood analysis an albuminemia of 10 g/l and proteinuria of 22 g/d was observed. A first renal biopsy was carried out which indicated minimal change disease. Steroid treatment was started, as a result the nephrotic syndrome disappeared and the blood analysis normalized. Later he had 4 new outbreaks, all of them steroid-responsive. In 1992 a second renal biopsy was performed after the fourth outbreak and the presence of mild renal failure, that this time indicated a IgA nephropathy. Steroid treatment was tried again, and this time cyclophosphamide was added to try to reduce steroid doses. This result in normalization of renal function and decrease of proteinuria to 2 g/d. The patient remained stable until 1996 when the fifth outbreak occurred, again with mild renal failure and proteinuria in nephrotic range. Therefore a third renal biopsy was performed, that confirmed the presence of IgA nephropathy, but now with signs of histological progression of the disease. Following this, he presented five outbreaks in 3 years, all of them steroid-responsive, with decrease of proteinuria although without renal function normalization. In the year 2000, at his tenth outbreak of nephrotic syndrome it was decided to add cyclosporine to the steroid treatment, achieving the stability of the patient, without further outbreaks until now, with proteinuria of 1.6 g/d and C. creat. 59 ml/min.

Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America.

Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. CASE PRESENTATION - CASE 1: A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. CASE 2: A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.

[Value of renal biopsy in the elderly. 32 cases].

Between November 1985 and November 1989, percutaneous renal biopsy was performed in 32 patients aged 75 or more (mean age 78). The major clinical presentations were nephrotic syndrome in 22 patients, variable amounts of proteinuria in 6 patients and unexplained severe renal insufficiency in 4 patients. In 27 cases the histological study revealed a glomerular disease. Minimal change disease (7 cases), membranous nephropathy (6 cases), amyloidosis (5 cases) and crescentic glomerulonephritis were the most frequent types. The rate of complications after biopsy was low (3 percent) with only one retroperitoneal hematoma. Owing to the atypical renal presentation of some glomerulopathies in the elderly, renal biopsy was useful to differentiate between minimal change disease, membranous nephropathy and amyloidosis. In 4 patients with minimal change disease, remission of nephrotic syndrome was obtained with corticosteroids. Moreover renal biopsy allowed to detect underlying diseases and gave indications to initiate specific therapy particularly in crescentic glomerulonephritis the outcome of which remained unfavourable. It is concluded that, even in elderly, renal biopsy is a valuable and safe diagnostic tool to obtain a rapid diagnosis, particularly in glomerular diseases, leading to a biopsy-guided therapy. It must therefore have the same indications as in younger adults with glomerular syndrome or rapidly progressive renal insufficiency.

[A case of renal cell carcinoma associated with rapidly progressive glomerulonephritis].

A 74-year-old man was admitted to our hospital because of a treatment for his right renal tumor. The abdominal CT scanning revealed a mass in the right kidney, and a right selective renal arteriography demonstrated a hypervascular tumor. On admission, urinalysis revealed proteinuria (3-4 g/day) and microscopic hematuria, and serum electrolytes were normal. Serum creatinine and urea nitrogen levels were 1.6 mg/dl and 30 mg/dl, respectively. A percutaneous right renal biopsy specimens showed crescentic glomerulonephritis. Direct immunofluorescence studies showed strong linear staining for IgG and IgA along the glomerular capillary walls. Electron microscopy showed increased mesangial matrix and swollen epithelial cells, but no dense deposits in the para-mesangial area and in the glomerular basement membrane. The patient underwent right radical nephrectomy. Histologic examination of the resected specimen revealed renal cell carcinoma. Postoperatively, he developed rapidly progressive renal failure and the renal function could not be recovered. Using the indirect immunofluorescence technique, we could not confirm the presence of a serum anti-glomerular basement membrane antibody, although the examination could not be carried out until the initiation of hemodialysis therapy. Some cases of glomerulopathies associated with renal cell carcinoma were previously reported, but the case of crescentic glomerulonephritis was very rare.

Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody.

A 56-year-old male with DM and HTN presented with flank pain and nausea. Review of systems was negative, physical examination was notable for mild hypovolemia and laboratory revealed BUN 51 mg/dl, creatinine (Cr) 5.1 mg/dl (baseline 1.5), Westergren ESR 122 mm/h, fractional excretion of sodium 0.2% and UA positive for blood and protein. Despite volume resuscitation the Cr continued to rise. Urine sediment analysis revealed granular casts, renal tubular epithelial cells and a negative Hansel's stain. Hemodialysis was initiated with Cr 13.7 mg/ dl for dyspnea and dysgeusia. Subsequent laboratory data revealed 2 separate positive anti-GBM antibody titers and prednisone therapy was initiated. Renal biopsy was performed for further diagnostic, therapeutic and prognostic information and demonstrated interstitial nephritis with linear IgG and albumin deposition consistent with diabetic nephropathy. Follow-up antibody titers were negative. prednisone was discontinued and Cr stabilized with conservative therapy. Anti-GBM antibody disease is characterized by circulating IgG antibodies directed against the glomerular basement membrane, specifically the alpha-3 (IV) collagen chain. Anti-GBM nephritis is a rapidly progressive, isolated glomerulonephritis in association with circulating anti-GBM antibodies. A positive immunofluorescence (IF) test is considered diagnostic in the appropriate clinical setting. Therapies include immunosuppressive agents to suppress new antibody production and plasmapheresis to eliminate circulating antibodies. Anti-GBM antibody is not rapidly cleared by steroid therapy and the recovery of renal function is rare if initiation Cr is greater than 7 mg/dl. This case demonstrates that the current ELISA for alpha-3 (IV) collagen is not pathognomonic for anti-GBM nephritis and that renal biopsy with IF for IgG and albumin may be indicated to prevent administration of potentially toxic treatment.

Anti-glomerular Basement Membrane Disease: A Rare Case Report of Changing Clinical Phenotype and Atypicalities.

A man in his late 20s, a smoker, presented with nephrotic-range proteinuria and mild renal failure. He had no macroscopic hematuria or decreased urine output. Kidney biopsy was done which revealed a surprising diagnosis of anti-glomerular basement membrane (anti-GBM) disease. He was started on intravenous methylprednisolone, plasma exchanges, and cyclophosphamide. His anti-GBM antibody was, however, weak positive. After five sessions of plasma exchange, he was discharged with a negative anti-GBM antibody. The patient defaulted drugs and presented with rapidly progressive renal failure and hemoptysis after 1½ months. The patient was started on intravenous methylprednisolone, hemodialysis, plasma exchanges, and cyclophosphamide. Repeat biopsy after stabilization was suggestive of anti-GBM disease with fibrocellular crescents. Anti-GBM antibody was negative. Although the patient presented with an estimated glomerular filtration rate of 10 mL/min/1.73 m<sup2</sup and fibrocellular crescents, the patient improved with treatment and was discharged with a serum creatinine of 2.2 mg/dL. This patient had two presentations: one with nephrotic-range proteinuria and mild renal failure, revealing anti-GBM disease on biopsy, and the second with rapidly progressing renal failure which improved with treatment. There were many atypical features in his presentation. Nonabstinence from smoking might be a triggering factor for the second episode. The pathological antibodies may be against a nonconventional epitope or poorly complement fixing, resulting in negative anti-GBM antibody and good recovery in spite of severe renal failure.

[Criteria to indicate kidney biopsy in type 2 diabetic patients with proteinuria: Survey among French nephrologists].

Diabetic nephropathy is usually a presumptive diagnosis based on clinical and biological evidence. Renal biopsies are performed in diabetic patients with atypical findings evoking non-diabetic renal disease who could benefit from specific therapies. French speaking nephrologists were asked which criteria they retain to indicate renal biopsy in patients with type 2 diabetes and albuminuria>0.5g/day or equivalent through an online anonymous questionnaire. Among the suggested criteria were absence of diabetic retinopathy, hematuria, rapid decrease in GFR, short diabetes duration or rapid raise of proteinuria. 188 people answered the poll among whom interns (12%), fellows (13%), university hospital practitioners (26%), general hospital practitioners (24%), practitioners in a non-profit organization (13%), practitioners on private activity (10%), multi-modal practitioners (3%) and people without clinical activity (2%). Increasing proteinuria was retained as an indication criterion for renal biopsy by 51% of respondents, nephrotic syndrome by 56% of respondents, absence of diabetic retinopathy by 57% of respondents, short diabetes duration by 65% of respondents, rapid GFR decline by 75% of respondents and hematuria by 78% of respondents. These data highlight the high diversity of opinions on this topic and their discrepancies with guidelines and current literature regarding the association between non-diabetic renal disease and clinical and biological features. The lack of adhesion of nephrologists to guidelines was especially noteworthy regarding the absence of diabetic retinopathy. These results emphasize the need for studies focusing on biopsy indication criteria in patients with type 2 diabetes.

Recurrent IgA nephropathy complicated with Crohn's disease after renal transplantation.

A 27-year-old man was diagnosed with IgA nephropathy and Crohn's disease. He had been diagnosed with proteinuria and hematuria since he was 20 years old. Diarrhea had been a continuing problem during the past 5 months. Neither corticosteroid therapy nor tonsillectomy was performed. Hemodialysis was required at age of 30, while the symptoms of Crohn's disease were ameliorated by an elemental diet. He received a renal transplant from his mother 4 months after starting dialysis therapy. The initial immunosuppression therapy consisted of methylprednisolone, mycofenolate mofetil, cyclosporine, and basiliximab. Eight months after transplantation, proteinuria and hematuria appeared and serum creatinine was 1.4 mg/dL. Relapse of IgA nephropathy was confirmed by the one-year protocol biopsy. He had suffered from tonsillitis at 32 months after the transplantation. Urinary protein increased to 3 g/day and serum creatinine was elevated to 2.04 mg/dL. Renal biopsy was performed 2 weeks after the urinary findings were aggravated. The cellular crescents constituted 36 % of the glomeruli. The findings of rejection were not confirmed in both biopsies. Tonsillectomy was performed thereafter. No additional immunosuppressive therapy was added. Proteinuria and hematuria disappeared at 4 and 20 months, respectively, after tonsillectomy, even when the symptoms of Crohn's disease worsened 69 months and 89 months after transplantation. A renal biopsy was performed 101 months after transplantation. Although IgA in the mesangium area was confirmed by immunohistochemical staining, no active lesion was seen. Tonsillectomy along with immunosuppressants for the graft might be an effective treatment for some patients with active recurrent IgA nephropathy.

A case of minimal change nephrotic syndrome with immunoglobulin A nephropathy transitioned to focal segmental glomerulosclerosis.

A 50-year-old woman with a 1-month history of lower extremity edema and a 5 kg weight increase was admitted to our hospital with suspected nephrotic syndrome in October 1999. Urine protein level was 3.5 g per day, 10-15 erythrocytes in urine per high-power field, and serum albumin level 2.5 g/dl. Furthermore, an accumulation of pleural effusion was confirmed by chest X-ray. The results of a renal biopsy indicated slight mesangial proliferation in the glomeruli by light microscopy, and an immunofluorescence study confirmed the deposition of immunoglobulin (Ig) A and C3 in the mesangial area. Diffuse attenuation of foot processes and dense deposits in the mesangial area were observed by electron microscopy. Treatment with 40 mg/day of prednisolone was effective, and proteinuria was negative 1 month later. Because of this course, we diagnosed minimal change nephrotic syndrome complicated by mild-proliferative IgA nephropathy. In November 2000, there was a relapse of nephrotic syndrome, which was believed to be induced by an influenza vaccination, but response to increased steroid treatment was favorable, and proteinuria disappeared on day 13 of steroid increase. A second relapse in May 2001, showed steroid resistance with renal insufficiency, and an increase in the selectivity index to 0.195. Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. Subsequently, her renal function gradually worsened to the point of end-stage renal failure by 27 months after the second relapse of nephrotic syndrome.

A Case of Membranous Nephropathy Hypothesized to be Associated With COVID-19 Vaccine.

A 56-year-old male patient with a medical history of essential hypertension was referred to the emergency room after he was found to have a serum creatinine level of 13 mg/dL at his primary care physician's office. The patient reported that he had developed a coronavirus disease 2019 (COVID-19)-like infection six months prior that was not confirmed. Two months later, he started to notice dyspnea on exertion and bilateral lower limb swelling and was started on furosemide. He received the first dose of the Moderna COVID-19 vaccine a month before the presentation but did not receive the second dose. Subsequently, his lower limb swelling and exertional dyspnea started worsening. He denied any new medication, dysuria, oliguria, hematuria, fever, or any other symptoms. Initial evaluation was consistent with kidney failure. Hypocalcemia and hyperphosphatemia were noted, along with medical renal disease on renal ultrasound. Eosinophils and nephrotic-range proteinuria were found in the urine. His serum phospholipase A2 receptor (PLA2R) antibodies were positive. A renal biopsy showed membranous glomerulonephritis with moderate segmental sclerosis, as well as tubulointerstitial fibrosis with neutrophils, consistent with acute interstitial nephritis. Positive staining for PLA2R in the glomerular deposits suggested primary membranous nephropathy (MN). He was treated with prednisone first, and when the kidney biopsy was conclusive for membranous glomerulopathy, he was started on rituximab. On admission, he received hemodialysis intermittently, but this was stopped a month after discharge as his renal function normalized. Recently, there have been numerous cases reported with new onset of glomerular disease after receiving the COVID-19 vaccine. Further studies of vaccinated patients are needed to determine whether the severe acute respiratory syndrome coronavirus 2 virus vaccination is associated with a higher risk of MN and to identify potential predisposing factors and mechanisms of kidney injury in patients in whom it occurs.