Dementia with visual hallucinations at the beginning of the course (in the first 2 years) is very suggestive of Lewy bodies, and is the guiding symptom in these questions. If we add to this the falls and motor slowing suggestive of parkinsonism, it makes the question easier. Therefore, number 3 is correct.

Dementia with visual hallucinations at the beginning of the course (in the first 2 years) is very suggestive of Lewy bodies, and is the guiding symptom in these questions. If we add to this the falls and motor slowing suggestive of parkinsonism, it makes the question easier. Therefore, [HIDDEN].

A 78-year-old male consults for a year-long history of progressive cognitive impairment with memory and orientation lapses. His family reports recurrent visual hallucinations, occasional falls and striking motor slowing. What is the most likely diagnosis?

Familial dementia with Lewy bodies with an atypical clinical presentation.

The authors report a case of a 64-year-old male with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB.

[Cognitive disorders appearing before the age of 65 in patients of the Alzheimer Centre of the VU Medical Centre: diagnoses and clinical characteristics].

To obtain a profile of the causes and clinical characteristics of cognitive disorders in patients referred to a memory clinic before the age of 65 years. Retrospective case-note study. Data were collected from 127 subjects with objective cognitive disorders who visited the Alzheimer Centre of the VU Medical Centre in Amsterdam, the Netherlands, in the period from 1 January 2001 to 31 December 2003 with an onset of complaints before the age of 65. Besides the diagnoses, we investigated the clinical presentations, the occurrence of cardiovascular risk factors, the family history, and the presence of noncognitive neurological signs. The most common causes of cognitive decline under the age of 65 were Alzheimer's disease (46%) and frontotemporal dementia (23%). Vascular dementia was seen in 5% and dementia with Lewy bodies in 2%; 9% had mild cognitive impairment but no dementia. Hypertension and a positive family history for dementia were each present in 40% of the patients. Non-cognitive neurological abnormalities were found only in cases of non-Alzheimer dementia. During the period under investigation, the number of patients with objective cognitive disorders increased more than did the number without a cognitive disorder. Within the population of a memory clinic, Alzheimer's disease was the most frequent cause of cognitive decline under the age of 65, followed by frontotemporal dementia. The distribution differed from causes of dementia at an older age, where vascular dementia had the second place.

Dementia with Lewy bodies

Frontotemporal dementias Corticobasal syndrome, corticobasal degeneration and progressive supranuclear palsy are frontotemporal dementias with features of parkinsonism and impaired cognition. Similar to DLB, imaging may show reduced dopamine transporter uptake. Corticobasal syndrome and degeneration, and progressive supranuclear palsy, are usually distinguished from DLB by history and examination. Motor movements in corticobasal syndrome are asymmetrical. There are differences in posture, gaze and facial expressions in the most common variants of progressive supranuclear palsy, and falling backwards is more common relative to DLB. Visual hallucinations and fluctuating cognition are unusual in corticobasal degeneration and progressive supranuclear palsy. Management

[Dementias with Lewy bodies].

Dementias with Lewy bodies are no rare cause of cognitive and motor impairments in old age. Neuropathologically, they must be distinguished into diffuse Lewy body disease resp. dementia with Lewy bodies, Parkinson's disease with concomitant Alzheimer's pathology, and the Lewy body variant of Alzheimer's disease according to extent and concomitant pathology. The most reliable diagnostic features of dementia with Lewy bodies are fluctuating disturbances of cognition and consciousness, visual disorders (hallucinations, visuoperceptive and visuoconstructive impairments), and early extrapyramidal signs of the hypokinetic-rigid type with a propensity to frequent falls. The pertinent diagnostic criteria are the consensus criteria according to McKeith et al. Additional contributions are to be expected by functional neuroimaging (SPECT, PET) and CSF examination (homovanillic acid). However, even assuming the most favorable conditions a diagnostic accuracy of 85 % is presently hard to achieve. Particularly, as is demonstrated using a case example, reliable antemortem diagnosis of Lewy body variant of Alzheimer's disease is hardly possible. Clinically, this group of diseases is important, since increased neuroleptic sensitivity must be taken into account and modern central cholinergic agents seem to be a promising therapeutic option.

Frontotemporal Dementia: Dilemma in Discrimination From Similarly Presenting Neurological and Psychiatric Conditions.

Frontotemporal dementia (FTD) is the most common cause of neurocognitive decline, second to Alzheimer's disease (AD) and Lewy body dementia. Its presence offers a unique challenge to physicians trying to detect cognitive deficits, as it not only arises in middle age but also can be misdiagnosed as a primary psychiatric disorder. The following case describes the clinical course of a 50-year-old male with a recent history of sporadic visual and auditory hallucinations, followed by a gradual decline in cognitive function including declining memory, apathy and behavioral disinhibition, and social functioning, which are suggestive of FTD-type. Apart from the gradual decline of his cognitive function, the patient had multiple clinical encounters, during which he was misdiagnosed with schizophrenia. Furthermore, the report showcases the handful of conditions that FTD can be misdiagnosed and discusses the thorough clinical/psychological examination and investigations to be done to arrive at FTD.

[Familial non-Alzheimer dementia].

This is an abstract of my lecture on familial non-Alzheimer dementia. 1. Vascular dementia 1) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by autosomal dominant inheritance, smooth muscle cell degeneration and granular osmiophilic material (GOM) in arterioles, and Notch 3 mutations. 2) CARASIL This is an autosomal recessive vascular dementia with unknown etiology. 3) Familial amyloid angiopathy Familial cerebral hemorrhage and dementia is caused by mutations in amyloid precursor protein, cystatin c, and Bri genes. 2. Familial non-Alzheimer degenerative dementia 1) Dementia with Lewy bodies This is characterized by Alzheimer like dementia, visual hallucination and diffuse Lewy bodies which are formed by ubiquitinated alpha-synuclein. Occasionally, familial forms are reported, but gene mutations are unknown. 2) Frontotemporal dementia (FTD) FTDP-17 is characterized by tau mutations, character and personal changes, and disinhibition. The gene mutations were also found in familial forms of Pick's disease, corticobasal degeneration, and other tauopathies. 3) Familial British dementia (FBD), familial Danish dementia (FDD) FBD and FDD are characterized by Abri amyloid deposits, amyloid angiopathy and dementia. Mutations in Bri gene are reported. 4) Familial encephalopathy with neuroserpin inclusion bodies (FENIB) FENIB is characterized by dementia, Collins body and neuroserpin gene mutation.

Dementia with Lewy bodies and the neurobehavioral decline of Mervyn Peake.

Mervyn Peake (1911-1968) was an accomplished British artist, poet, novelist, and playwright. He was a prolific and talented illustrator and wrote hundreds of poems, 4 novels, and several plays. His exceptional career was prematurely ended by a neurodegenerative illness variously ascribed to Alzheimer disease, Parkinson disease, or postencephalitic parkinsonism. However, a detailed review of biographical accounts produces substantial evidence in support of a probable diagnosis of dementia with Lewy bodies, a clinical entity remaining undiagnosed outside specialty dementia clinics. Peake developed signs of parkinsonism and insidious cognitive decline during his fifth decade. A breakdown in his writing style has frequently been cited as reflecting his encroaching dementia. Visual hallucinations are portrayed in sketches, and together with paranoid delusions are apparent in poetry composed during his illness. His deterioration was progressive and punctuated by well-described episodes of confusion and psychosis. His occasional preservation of insight is poignantly captured in drawings of figures with dunce caps or pointed heads, often with expressions of fear and apprehension etched with an economy of strokes. Peake spent his final years in various psychiatric institutions but continued to exhibit lucid intervals even late into his illness. His tragic deterioration remained undiagnosed at the time, but in retrospect, his progressive dementia with parkinsonism, visual hallucinations, and marked cognitive fluctuations likely represents one of the earliest recognized historical cases of dementia with Lewy bodies.

[Frontal dementia or dementia praecox? A case report of a psychotic disorder with a severe decline].

Many authors have described these last years the difficulty to establish a differential diagnosis between schizophrenia and frontotemporal dementia. However treatment and prognosis of these two separate diseases are not the same. Schizophrenia is a chronic syndrome with an early onset during teenage or young adulthood period and the major features consist of delirious ideas, hallucinations and psychic dissociation. However a large variety of different symptoms describes the disease and creates a heterogeneous entity. The diagnosis, exclusively defined by clinical signs, is then difficult and has led to the research of specific symptoms. These involve multiple psychological processes, such as perception (hallucinations), reality testing (delusions), thought processes (loose associations), feeling (flatness, inappropriate affect), behaviour (catatonia, disorganization), attention, concentration, motivation (avolition), and judgement. The characteristic symptoms of schizophrenia have often been conceptualised as falling into three broad categories including positive (hallucination, delision), negative (affective flattening, alogia, avolition) and disorganised (poor attention, disorganised speech and behaviour) symptoms. No single symptom is pathogonomonic of schizophrenia. These psychological and behavioural characteristics are associated with a variety of impairments in occupational or social functioning. Cognition impairments are also associated with schizophrenia. Since the original clinical description by Kraepelin and Bleuler, abnormalities in attentional, associative and volitional cognitive processes have been considered central features of schizophrenia. Long term memory deficits, attentional and executive dysfunctions are described in the neurocognitive profile of schizophrenic patients, with a large degree of severity. The pathophysiology of schizophrenia is not well known but may be better understood by neuronal dysfunctions rather than by a specific anatomical abnormality. Frontotemporal lobar degeneration (FTLD) is one of the most common causes of cortical dementia. FTLD is associated with an anatomical atrophy that can be generalised, with a frontotemporal or focal lobar predominance. Histologically there is severe neuronal loss, gliosis and a state of spongiosis. In a minority of case Pick cells and Pick bodies are also found. The usual clinical features of FTLD are divided in three prototypic syndromes: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). FTD is the most common clinical manifestation of FTLD. FTD is first characterised by profound alteration in personality and social conduct, characterised by inertia and loss of volition or social disinhibition and distractibility. There is emotional blunting and loss of insight. Speech output is typically economical, leading ultimately to mutism, although a press of speech may be present in some overactive, disinhibited patients. Memory is relatively preserved in the early stage of the disease. Cognitive deficits occur in the domains of attention, planning and problems solving, whereas primary tools of language, perception and spatial functions are well preserved. PA is an initial disorder of expressive language, characterised by effortful speech production, phonologic and grammatical errors. Difficulties in reading and writing also occur but understanding of word meaning is relatively well preserved. In SD a severe naming and word comprehension impairment occur on the beginning in the context of fluent, effortless, and grammatical speech output. There is also an inability to recognise the meaning of visual percepts. The clinical syndromes of FTLD are associated with the brain topography of the degeneration. So considerable clinical overlap can exist between schizophrenia and FTLD and the object of the following case report is to remind the difficulty to make a differential diagnosis between these two pathologies. A 34 year old non-married man is admitted in mental health district of a general hospital for behavioural disturbances that include repeated aggressions towards his family. At initial interview visual and auditives hallucinations are described. The patient doesn't care about these abnormalities and a poverty of speech is observed. The affects, globally blunted, show some degree of sadness however. The patient's birth and early development were unremarkable. At the age of 26, the patient dismissed from his job because of poor performance and absenteeism. He spent a lot of time watching TV, showed poverty of speech and become sometimes angry and violent without an explanation. He was hospitalised for several months and a schizophrenia including predominant negative features, hallucinations and delusion was diagnosed. He was treated with bromperidol, could go back to home and was followed by a general practitioner for 8 years. The patient had a stereotyped way of life during these years with a poor communication and little activity. During the months preceding the current hospitalisation, these characteristics and avolition emphasised, urinary incontinence appeared. The patient receives risperidone 8 mg/day associated with citalopram 40 mg/day during several months of hospitalisation. No significant evolution is observed regarding apathic and stereotyped way of live. The capacity of communication remains very poor. Neurocognitive assessments reveal multiple and severe dysfunctions. Memory, executive and attentional tasks are extremely disturbed. Physical and neurological examinations reveal an isolated bilateral Babinski sign. Cerebral scanner and magnetic resonance show bifrontal atrophy and PET scan is normal. There are no significant abnormalities found on blood and urine samples and on lumbar puncture. The patient is sent to a chronic neuropsychiatric hospital and the treatment is stopped. One year later, a comparative evaluation is realised. The general clinical state shows no evolution. Neurocognitive assessments are repeated and severe dysfunctions are observed with more perseverations. A diagnosis of FTLD for this patient can be discussed regarding clinical features, neurocognitive testings and neuroradiological findings. Schizophrenia is a major differential diagnosis. Psychotic symptoms like hallucinations and age of onset are essential observations for the diagnosis of schizophrenia but can not exclude FTLD. Memory, intellectual functions, executive and attentional abilities may all be disturbed in schizophrenia and FTLD. Cerebral abnormalities well established in schizophrenia are lateral ventricles enlargements. Frontal lobar atrophy is a major argument for FTLD and is only a sporadic finding in schizophrenic populations. Schizophrenia and FTLD could be comorbid diseases by several ways. A differential diagnosis between schizophrenia and FTLD is difficult to establish. Schizophrenia is a heterogeneous disease with a large variety of cognitive dysfunctions. Neurocognitive tools may improve our knowledge of schizophrenia.

Dementia

The most common type of dementia is Alzheimer's disease. Other common types include vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Less common causes include normal pressure hydrocephalus, Parkinson's disease dementia, syphilis, HIV, and Creutzfeldt–Jakob disease.

Differentiating dementias in long-term care patients.

Many long-term care residents are diagnosed with dementia, but dementia appears in many forms. Alzheimer's disease, the most common, is typified by a slow onset and relentless progression to complete incapacitation. Vascular dementia usually appears somewhat abruptly, is associated with vascular comorbidities, and has an unpredictable progression pattern. Lewy body dementia shares features of both Alzheimer's and Parkinson's disease; its hallmarks include fluctuating cognitive performance, visual hallucinations, and extrapyramidal motor symptoms. Frontotemporal dementias are associated less with memory disorders and more with behavioral and language aberrations. Mixed dementia covers those patients who do not have an apparent singular cause of dementia. Pseudodementia is a dementia resulting from underlying causes and is reversible, unlike the aforementioned dementias.

Early onset dementia

Early onset dementia is dementia in which symptoms first appear before the age of 65. The term favored until about 2000 was presenile dementia; young onset dementia is also used. Early onset dementia may be caused by degenerative or vascular disease, or it may be due to other causes, such as alcohol-related dementia and other inflammatory or infectious processes. Early-onset Alzheimer's disease, vascular dementia and frontotemporal lobar degeneration are the most common forms of early onset dementia, with Alzheimer's accounting for between 30 and 40%. Early onset dementia may also occur, less frequently, in the Lewy body dementias (dementia with Lewy bodies and Parkinson's disease dementia), multiple sclerosis, Huntington's disease and other conditions. References Further reading Cognitive disorders Dementia

Pathology and temporal onset of visual hallucinations, misperceptions and family misidentification distinguishes dementia with Lewy bodies from Alzheimer's disease.

To determine whether the temporal onset of visual phenomena distinguishes Lewy body disease (LBD) from Alzheimer's disease (AD), and to characterize the extent Lewy bodies and neurofibrillary tangles are associated with these clinical features. Consecutive cases of autopsy-confirmed LBD (n = 41), AD (n = 70), and AD with amygdala-predominant Lewy bodies (AD-ALB) (n = 14) with a documented clinical history of dementia were included. We mailed questionnaires to next-of-kin asking about symptoms during life. Lewy pathology and neurofibrillary tangle pathology were assessed. The occurrence of visual hallucinations, misperceptions and family misidentification did not distinguish LBD from AD or AD-ALB, but the onset was earlier in LBD compared to AD and AD-ALB. When visual hallucinations developed within the first 5 years of dementia, the odds were 4-5 times greater for autopsy-confirmed LBD (or intermediate/high likelihood dementia with Lewy bodies) and not AD or AD-ALB. In LBD, limbic but not cortical Lewy body pathology was related to an earlier onset of visual hallucinations, while limbic and cortical Lewy body pathology were associated with visual misperceptions and misidentification. Cortical neurofibrillary tangle burden was associated with an earlier onset of misidentification and misperceptions in LBD and AD, but only with earlier visual hallucinations in AD/AD-ALB. When visual hallucinations occur within the first 5 years of the dementia, a diagnosis of LBD was more likely than AD. Visual hallucinations in LBD were associated with limbic Lewy body pathology. Visual misperceptions and misidentification delusions were related to cortical Lewy body and neurofibrillary tangle burden in LBD and AD/AD-ALB.

Cognitive-behavioral profiles of neurodegenerative dementias: beyond Alzheimer's disease.

The neurocognitive and behavioral profiles of vascular dementia and vascular cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia, and dementia syndromes associated with frontotemporal lobar degenerations are compared and contrasted with Alzheimer's dementia (AD). Vascular dementia/vascular cognitive impairment is characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Dementia with Lewy bodies and Parkinson's disease with dementia are equally contrasted with AD by defective processing of visual information, better performance on executively supported verbal learning tasks, greater attentional variability, poorer qualitative executive functioning, and the presence of mood-congruent visual hallucinations. The frontal variant of frontotemporal lobar degeneration (frontotemporal dementia) differs from AD by better multimodal retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. For temporal variants of frontotemporal lobar degenerations, progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic.

Dementia with Lewy bodies showing advanced Lewy pathology but minimal Alzheimer pathology--Lewy pathology causes neuronal loss inducing progressive dementia.

The present study concerns an autopsied case of dementia with Lewy bodies (DLB) showing advanced Lewy pathology but minimal Alzheimer pathology. The patient was a 50-year-old Japanese male without inheritance. His initial symptoms at the age of 43 suggested the diagnosis ofjuvenile idiopathic Parkinson's disease (PD), but were followed by memory disturbance 1 year later. He showed parkinsonism, dementia, personality change, fluctuating cognition and visual hallucinations 3 years later. Neuroradiological examination revealed moderate brain atrophy, predominantly in the frontal and temporal lobes. Neuropathological examination demonstrated a widespread occurrence of Lewy bodies (LB) with LB-related neurites not only in the brainstem but also in the cerebrum. The present case showed Lewy pathology which corresponded to stage IV by our staging and was parallel to neuronal loss. There was marked neuronal loss with many LB-related neurites in the CA2 of the hippocampus. Neurofibrillary tangles (NFT) were almost restricted to the entorhinal cortex, while senile plaques were absent. Consequently, the present case was pathologically diagnosed as having DLB of the neocortical type, pure form. In the present study, we suggest that Lewy pathology in the cerebral cortex could be responsible for progressive dementia.

Parkinson-Plus Syndrome -- History and Physical -- Lewy Body Dementia

LBD consists of dementia characterized by deficits in attention, cognition, and visuospatial function. Other notable features include visual hallucinations, rapid eye movement sleep behavior disorder (RBD), repeated falls, autonomic dysfunction, antipsychotic drug sensitivity, delusions, and depression. LBD consists of two clinical entities: dementia with Lewy bodies and PD dementia. Dementia with Lewy bodies is classified as dementia occurring first or within one year of the movement disorder. PD dementia occurs in a patient first receiving the diagnosis of PD and then developing dementia symptoms after one year or more of the diagnosis. [20]

Visual signs and symptoms of dementia with Lewy bodies.

Dementia with Lewy bodies ('Lewy body dementia' or 'diffuse Lewy body disease') (DLB) is the second most common form of dementia to affect elderly people, after Alzheimer's disease. A combination of the clinical symptoms of Alzheimer's disease and Parkinson's disease is present in DLB and the disorder is classified as a 'parkinsonian syndrome', a group of diseases which also includes Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy. Characteristics of DLB are fluctuating cognitive ability with pronounced variations in attention and alertness, recurrent visual hallucinations and spontaneous motor features, including akinesia, rigidity and tremor. In addition, DLB patients may exhibit visual signs and symptoms, including defects in eye movement, pupillary function and complex visual functions. Visual symptoms may aid the differential diagnoses of parkinsonian syndromes. Hence, the presence of visual hallucinations supports a diagnosis of Parkinson's disease or DLB rather than progressive supranuclear palsy. DLB and Parkinson's disease may exhibit similar impairments on a variety of saccadic and visual perception tasks (visual discrimination, space-motion and object-form recognition). Nevertheless, deficits in orientation, trail-making and reading the names of colours are often significantly greater in DLB than in Parkinson's disease. As primary eye-care practitioners, optometrists should be able to work with patients with DLB and their carers to manage their visual welfare.

Lewy body dementias

Classification The synucleinopathies (dementia with Lewy bodies, Parkinson's disease dementia, and Parkinson's disease) are characterized by shared features of parkinsonism motor symptoms, neuropsychiatric symptoms, impaired cognition, sleep disorders, and visual hallucinations. The Lewy body dementias—dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD)—are distinguished by the timing when cognitive and motor symptoms appear. The two Lewy body dementias are often considered to belong on a spectrum of Lewy body disease that includes Parkinson's disease. MeSH lists Lewy body disease in several categories: as a nervous system disease in two listings one as a basal ganglia Parkinsonian movement disorder and the other under brain disease as a dementia; as a neurodegenerative disorder listed as a synucleinopathy; and as a neurocognitive disorder listed with dementia. Cause and mechanisms

Dementia with Lewy bodies

Essential feature A dementia diagnosis is made after cognitive decline progresses to a point of interfering with normal daily activities, or social or occupational function. While dementia is an essential feature of DLB, it does not always appear early on, and is more likely to present as the condition progresses. Core features While specific symptoms may vary, the core features of DLB are fluctuating cognition, alertness or attention; REM sleep behavior disorder; one or more of the cardinal features of parkinsonism, not due to medication or stroke; and repeated visual hallucinations. The 2017 Fourth Consensus Report of the DLB Consortium determined these to be core features based on the availability of high-quality evidence indicating they are highly specific to the condition.

[Neuropsychological tests of simple application for diagnosing dementia].

Thirty patients with dementia defined by DSM-III-R criteria (Alzheimer's disease (22), vascular dementia (3), Parkinson's disease, frontal lobe dementia, possible diffuse Lewy body dementia, normal pressure hydrocephalus and uncertain diagnosis), with scores below 24 points in the Mini-Mental Status Examination and more than 4 years of education were submitted to a neuropsychological evaluation. The scores in the neuropsychological tests were compared to those obtained by thirty normal volunteers paired for age, sex and education. Sensitivity, specificity and accuracy of the tests in the distinction of demented and normal volunteers were determined. The accuracies were calculated using ROC curves. Blessed's information-memory-concentration test showed greatest accuracy, followed by copy of simple figures, delayed memory of 10 figures (after 5 minutes), recognition of 10 figures and verbal fluency test (animals). A linear discriminant function, composed by 6 tests: visual perception, incidental memory, delayed memory (after 5 minutes), drawing of a clock, verbal fluency (animals) and calculation tests, was able to discriminate all controls from patients and only one patient was wrongly classified as normal control. These tests were chosen because they can be applied in less than 10 minutes and are very easy to interpret. This discriminant function must be applied in another group of patients and controls in order to demonstrate its value. When associated to the MMSE it may be useful to discriminate patients with dementia from normal people in epidemiological studies.

The evolution and pathology of frontotemporal dementia.

This is a clinicopathologic study of a prospective, clinic-based cohort of patients with frontotemporal dementia (FTD)/Pick complex, who were followed to autopsy. A total of 60 patients with the clinical syndromes of the behavioural variant of FTD (FTD-bv) (n = 32), primary progressive aphasia (PPA) (n = 22), corticobasal degeneration syndrome (CBDS) (n = 4) and progressive supranuclear palsy (PSP) (n = 2) at onset, referred to a cognitive neurology clinic who had subsequent post-mortem examination were included. The most common histological variety was motor neurone disease type inclusion (MNDI) (n = 18), followed by corticobasal degeneration (CBD) (n = 12), then Pick's disease (n = 6), dementia lacking distinctive histology (DLDH) (n = 6) and PSP (n = 3). Others fulfilled the histological criteria for Alzheimer's disease combined with glial pathology (n = 6), Alzheimer's disease only (n = 4), Lewy body variant (n = 2), prion disease (n = 1), vascular dementia (n = 1) and undetermined (n = 1). The most common first syndrome among the MNDI and DLDH (tau negative) pathologies was FTD-bv, but subsequently progressive aphasia (PA), occasionally CBDS and semantic dementia also developed. Tau positive histologies of CBD, PSP and Pick bodies were most frequently associated with PPA onset or CBDS/PSP, but behavioural symptoms were also common. Age of onset was earlier in tau negative cases, but the duration of illness and gender distribution were about the same in all histological variants. Although the tau negative and positive histologies are predicted to some extent by the clinical onset, the extent of the overlap and the convergence of the syndromes in the course of the disease argue in favour of maintaining the clinical and pathological varieties under a single umbrella.

Dementia

Many other medical and neurological conditions include dementia only late in the illness. For example, a proportion of patients with Parkinson's disease develop dementia, though widely varying figures are quoted for this proportion. When dementia occurs in Parkinson's disease, the underlying cause may be dementia with Lewy bodies or Alzheimer's disease, or both. Cognitive impairment also occurs in the Parkinson-plus syndromes of progressive supranuclear palsy and corticobasal degeneration (and the same underlying pathology may cause the clinical syndromes of frontotemporal lobar degeneration). Although the acute porphyrias may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a type of dementia that primarily affects people in their 80s or 90s and in which TDP-43 protein deposits in the limbic portion of the brain.

Unusual features of Creutzfeldt-Jakob disease followed-up in a memory clinic.

Sporadic Creutzfeldt-Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety-depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.

Miliary brain metastases presenting as rapidly progressive dementia.

We report the case of a 79-year-old woman who developed a rapidly progressive dementia (RPD) with severe memory impairment, early visual hallucinations and extrapyramidal signs. Symptoms started suddenly after hip replacement surgery following an accidental fall. Motor epileptic seizures appeared at the end of the illness. Dementia worsened gradually leading to akinetic mutism. She died five and a half months after the onset of symptoms. MRI showed cerebral atrophy but failed to detect any other lesion. Results of all laboratory tests performed were negative. After the most frequent treatable diseases were excluded, the diagnosis of dementia with Lewy bodies was initially considered. CJD was also suggested based on the rapid evolution of the disease and the positivity of 14-3-3 protein in CSF. Neuropathological examination revealed an extensive miliary metastatic dissemination from an unknown primary adenocarcinoma. Pulmonary origin was suggested according to the immunohistochemical profile. Histopathological changes of Alzheimer's disease were also observed in the cerebral cortex and hippocampus. Neither Lewy bodies nor PrP deposits were found. The sudden onset of the dementia just after the hip replacement surgery raises the possibility of a pathological fracture with secondary tumoral microembolic dissemination. Despite its rarity, this entity should be included in the differential diagnosis of RPD. This case illustrates the definite importance of neuropathological post-mortem examination in order to elucidate the different types of dementia.

Frontotemporal dementia

See also Alcoholic dementia Lewy body dementia Logopenic progressive aphasia Mini-SEA Proteopathy Transportin 1 Vascular dementia References Further reading External links OMIM on Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis and Chromosome 9 Open Reading Frame 72; C9ORF72 Cognitive disorders Dementia Frontal lobe Temporal lobe de:Frontotemporale Demenz

Clinical Manifestations of Early-Onset Dementia With Lewy Bodies Compared With Late-Onset Dementia With Lewy Bodies and Early-Onset Alzheimer Disease.

Early-onset dementia, presenting in individuals younger than 65 years, is a diagnosis with significant social and financial implications. The early-onset form of dementia with Lewy bodies (DLB) is poorly understood. To investigate clinical features that distinguish early-onset DLB (onset and diagnosis at age <65 years) from late-onset DLB (onset at age ≥65 years) and from early-onset Alzheimer disease (AD) dementia. This is a retrospective case-control study on patients with pathologically confirmed DLB or AD enrolled in the National Alzheimer's Coordinating Center database from January 2005 to July 2017. The National Alzheimer's Coordinating Center Uniform Data Set comprised deidentified data collected by Alzheimer disease centers in the United States. Of patients fulfilling criteria for all-cause dementia at enrollment (n = 1152), those who at post mortem received a pathological diagnosis of either AD (n = 848) or Lewy body disease (n = 218) were selected. Excluding 52 patients owing to missing data and 12 diagnosed with Parkinson disease dementia, remaining patients were classified by age of symptom onset into early-onset AD, early-onset DLB, and late-onset DLB subgroups. Data were analyzed from June to December 2018 and from November to December 2021. Demographics, cognitive, behavioral, and motor features recorded at first clinic visit and neuropathological characteristics at autopsy were analyzed by disease subgroup. Concordance between initial etiologic diagnosis of dementia and final pathological diagnosis was assessed, as was time to death. A total of 542 individuals were categorized as having early-onset AD (n = 363; mean [SD] age, 53.0 [5.8] years; 208 [57.3%] male), early-onset DLB (n = 32; mean [SD] age, 57.9 [3.2] years; 23 [71.9%] male), and late-onset DLB (n = 147; mean [SD] age, 73.5 [5.5] years; 103 [70.1%] male). Early-onset DLB was clinically misdiagnosed in 16 individuals (50%). Features that predicted a diagnosis of early-onset DLB over early-onset AD included visual hallucinations (15 [46.9%] vs 42 [11.6%]), slowness (23 [71.9%] vs 95 [26.2%]), apathy (23 [71.9%] vs 189 [52.1%]), and motor deterioration that preceded cognitive and behavioral symptoms (7 [21.9%] vs 6 [1.7%]). Late-onset DLB had more amnestic features, but this was accounted for by a higher proportion of neocortical neuritic plaques and diffuse plaques (frequent in 79 [53.7%] vs 8 [25%]) than seen in early-onset DLB. This study found that early-onset DLB has clinical features that distinguish it from early-onset AD, whereas features of late-onset DLB are associated with a higher burden of AD copathology.

Lewy Body Dementia -- Introduction

There continues to be a debate between the relationship between Parkinson disease and LBD. The latest LBD consortium has set an arbitrary 12-month rule to differentiate LBD from Parkinson disease with dementia. If the patient has Parkinson disease for 12 months or longer before any cognitive impairment is noticed, then the disorder is most likely Parkinson disease with dementia, if the time period is shorter then the disorder is LBD. In most cases of LBD, dementia precedes the motor signs, particularly episodes of diminished responsiveness and visual hallucinations.

Differential diagnosis of Alzheimer's disease.

Accurate diagnosis of dementia is essential to provide appropriate treatment as well as patient and family counseling. It may be difficult to differentiate dementia from delirium. In addition, several features distinguish dementia from depression, but the two can coexist and the distinction may be uncertain. Dementias can be grouped into two categories: dementia that presents without prominent motor signs and dementia that presents with prominent motor signs. Dementias without prominent motor signs include Alzheimer's disease, frontotemporal dementia, and Creutzfeld-Jakob and other prion diseases. Dementias characterized at onset by prominent motor signs include dementias with Lewy bodies, idiopathic Parkinson's disease, progressive supranuclear palsy, cortico-basal ganglionic degeneration, hydrocephalus, Huntington's disease, and vascular dementia. Routine diagnostic steps include a careful history, mental status screening, laboratory and imaging studies, and neuropsychologic testing. Genetic testing is available, but its use is controversial and raises complex ethical questions.

Diagnostic diversity among patients with cognitive complaints: A 3-year follow-up study in a memory clinic.

To describe the distribution and estimate the mortality risks of degenerative dementias and nondegenerative conditions in a memory clinic. We enrolled 727 consecutive patients with cognitive complaints who visited the memory clinic in Buddhist Tzu Chi General Hospital during 2013 to 2016. Three main diagnostic groups were defined: pure type dementia, in which only one type of dementia was diagnosed, such as Alzheimer disease (AD), vascular dementia (VaD), Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD); mixed type dementia; and nondegenerative conditions. We described the frequency of different diagnoses and employed Cox proportional hazards regression models to examine the mortality risks for each diagnostic group after adjusting for age, sex, education, and cognitive status. All patients alive on or after September 30, 2018, were censored in the analysis. Two-thirds of patients (n = 496, 68.2%) were diagnosed with degenerative dementias. Pure type to mixed type dementia ratio was about 2: 1. AD remained the most common pure dementia subtype, followed by VaD and PDD. Among all nondegenerative conditions, depression/anxiety and subjective cognitive decline were the most common diagnoses. During a mean follow-up of 3.4 years, 150 deaths were documented, and the mortality risk was 61 deaths/1000 person-years. Mortality risks were associated with age, sex, education, and cognitive function at diagnosis but did not differ by diagnostic group. Clinical diagnoses for patients with cognitive complaints are diverse, and nearly one-third are of nondegenerative conditions. Baseline cognitive function is a stronger predictor for survival than clinical diagnosis.

Dementia

In some types of dementia, such as dementia with Lewy bodies and frontotemporal dementia, personality changes and difficulty with organization and planning may be the first signs. Middle As dementia progresses, initial symptoms generally worsen. The rate of decline is different for each person. MMSE scores between 6–17 signal moderate dementia. For example, people with moderate Alzheimer's dementia lose almost all new information. People with dementia may be severely impaired in solving problems, and their social judgment is usually also impaired. They cannot usually function outside their own home, and generally should not be left alone. They may be able to do simple chores around the house but not much else, and begin to require assistance for personal care and hygiene beyond simple reminders. A lack of insight into having the condition will become evident.

[Dementia with Lewy bodies].

Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, Parkinson syndrome, fluctuations of cognitive functions, vigilance and attention, visual hallucinations (usually detailed and well described), depression, REM-sleep behavior disorder, adverse responses to standard doses of neuroleptics, falls, syncopes, systematized delusions, and non-visual hallucinations. Mean age at disease onset ranges between 60 and 68 years. Male persons are more frequently affected than female. Disease duration is six to seven years. The differential diagnoses of DLB are dementia of the Alzheimer-type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and, in rare cases, Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha-receptor-blocking medicaments to improve neurogenic bladder dysfunction.

Dementia with Lewy bodies

Differential Many neurodegenerative conditions share cognitive and motor symptoms with dementia with Lewy bodies. The differential diagnosis includes Alzheimer's disease; such synucleinopathies as Parkinson's disease dementia, Parkinson's disease, and multiple system atrophy; vascular dementia; and progressive supranuclear palsy, corticobasal degeneration, and corticobasal syndrome. The symptoms of DLB are easily confused with delirium, or more rarely as psychosis; prodromal subtypes of delirium-onset DLB and psychiatric-onset DLB have been proposed. Mismanagement of delirium is a particular concern because of the risks to people with DLB associated with antipsychotics. A careful examination for features of DLB is warranted in individuals with unexplained delirium. PET or SPECT imaging showing reduced dopamine transporter uptake can help distinguish DLB from delirium.

Dementia

Imaging A CT scan or MRI scan is commonly performed to possibly find either normal pressure hydrocephalus, a potentially reversible cause of dementia, or connected tumor. The scans can also yield information relevant to other types of dementia, such as infarction (stroke) that would point at a vascular type of dementia. These tests do not pick up diffuse metabolic changes associated with dementia in a person who shows no gross neurological problems (such as paralysis or weakness) on a neurological exam. The functional neuroimaging modalities of SPECT and PET are more useful in assessing long-standing cognitive dysfunction, since they have shown similar ability to diagnose dementia as a clinical exam and cognitive testing. The ability of SPECT to differentiate vascular dementia from Alzheimer's disease, appears superior to differentiation by clinical exam.


In the male, the onset of puberty is considered normal from the age of 9 years, therefore in this case it is a premature puberty. The onset of puberty is defined as an increase in testicular volume (greater than or equal to 4cc); by specifying that the testicular size has not increased, we can rule out options 1 and 2. The excessive secretion of androgens produced by an adrenal tumor would cause a greater amount of hair and an increase in penile size, which our patient does not present. Therefore, the correct option is early adrenarche.

In the male, the onset of puberty is considered normal from the age of 9 years, therefore in this case it is a premature puberty. The onset of puberty is defined as an increase in testicular volume (greater than or equal to 4cc); by specifying that the testicular size has not increased, we can rule out options 1 and 2. The excessive secretion of androgens produced by an adrenal tumor would cause a greater amount of hair and an increase in penile size, which our patient does not present. Therefore, the [HIDDEN] option is early adrenarche.

An 8-year-old boy consults for the appearance of pubic hair at the base of the penis for the last 12 months. The testicle has not increased in volume and the penis has not increased in size. There is no increase in growth rate in the last year. The bone age is one year older than the chronological age. What is the most likely diagnosis?

Boy with central precocious puberty probably due to a peripheral cause.

A 6½ years Indian boy was brought by his parents, who were anxious about the excessive increase in the size of the boy's phallus, from the age of 2 years. On physical examination, the child had a penis length greater than the 97th centile for age, a sexual maturity rating of gonads at stage 2 and pubic hair at stage 3, with height in the high normal range (90-97th centile). The bone age was 12 years. Laboratory evaluation showed pubertal levels of testosterone and pubertal gonadotropin response to stimulation, confirming central precocious puberty (CPP). Incidentally, the hormonal profile also suggested congenital adrenal hyperplasia (CAH). This case report depicts a case of CPP probably caused by CAH in boys, which is rare.

[Precocious puberty and von Recklinghausen's disease].

Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

Hypothalamic hamartoma with precocious puberty: a case report.

Hypothalamic hamartoma (HH) is one of the most important causes of central precocious puberty in male children. Hamartomas are malformations composed of ectopic gonadotropic hormone (GnRH) neurons which secrete pulsatile gonadotropin releasing hormone. They are generally observed in children under 3 years. A case of 11/3 year-old male child presented with premature development of secondary sexual characters i.e., growth of pubic and axillary hair, enlargement of penis and acne over the face for the last 5 months. On physical examination, his height was 1.02 m and his weight 18kg, enlarged penile length of which 58mm; testicles were enlarged in size right one measuring 32X25mm and the left 30X23mm. His hematological and other biochemical investigations revealed no abnormality. Plain radiographic examination revealed radiological bone age of about 8-9 years. Endocrinological findings were as follows: Follicle stimulating hormone (FSH): 1.5mIU/ml, Luteinizing hormone (LH): 9.1mIU/ml, Testosterone: 701ng/dl (Testosterone level less than 30ng/dl in prepubertal age). Thyroid function tests were normal. Patient showed no adrenal pathology on ultrasound and his testicular parenchyma was homogeneous echotexture with the size of 30X22X16mm on the right (volume 5.4ml) and 30X20X15mm on the left (volume 4.6ml). With above physical & endocrinological findings and age of the child, it was suspected as a case of central precocious puberty. Subsequently MR imaging of the brain done & showed an oval non-enhancing pedunculated hypothalamic mass arising from the tubercinereum that was iso to hypointense to brain parenchyma on T1 - and intermediate signal on T2-weighted images, 20X10X10mm in diameter, extending into suprasellar cistern. During follow up after 06 months of starting conservative medication with gonadotropin-releasing hormone (GnRH) analog (Leuprolide acetate), his progression of puberty has been arrested and the testosterone level 18ng/dl, which is normal for his age.

Precocious Pseudo-Puberty with Testicular Enlargement: Two Cases of Leydig Cell Tumor with Different Histopathological Results.

Leydig cell tumors (LCT) are the most common hormone-secreting testicular tumors; it is a rare cause for precocious pseudo-puberty in boys. The tumors secrete high amounts of testosterone. We present two cases of LCT in prepubertal boys presenting with precocious puberty. Case 1. A 6-year-old boy was referred from the pediatric department with a diagnosis of precocious puberty. The patient had reported enlarged and painless swelling of the left testicle from a year ago. The puberty status of the patient was A1P3G4. Ultrasonography examination had found left testicular mass. Elective radical orchiectomy of the left testicle was performed. Histopathological analysis confirmed the diagnosis of benign LCT. Case 2. A 6-year-old boy presented with an enlarged left testicle for the last three months. Features of puberty were noted on the patient (appearance of pubic and facial hair). The puberty status of the patient was A1P3G3. Left testicle US had found homogenous, hypoechoic mass with calcification. Bone age had found increased bone maturation. Increased androgen hormones were detected through a blood test. Radical orchiectomy of the left testicle was performed. The histopathological examination showed malignant LCT. Leydig cell tumors uncommonly occur in children. Prepubertal-aged boys presented with asymmetrical, firm, painless testicular enlargement with signs of puberty should be evaluated for LCT. Histopathological analysis is the mainstay of diagnosis and radical orchiectomy is the treatment of choice of LCT.

[Clinical thinking and decision making in practice. A 7-year old boy with rapid growth and pubic hair].

A 7-year-old boy was tall, with a developing penis and initial growth of pubic hair. Due to the accelerated growth there was no premature adrenarche and due to the increased testicular volume there must have been a central cause for the production of androgens. Further specific investigations revealed an astrocytoma of the hypothalamus. After radiotherapy, the tumour exhibited no growth. The pubertal development was inhibited and the growth later stimulated by means of medication. In the case of pubertas praecox the growth chart and pubertal stages including testicular volume can help to differentiate between central and peripheral precocious puberty, narrow the diagnostic evaluation and reduce the time of the initial therapy.

Age at first conscious ejaculation: a milestone in male puberty.

The age of occurrence of the first conscious ejaculation was registered in 263 boys belonging to two categories: (1) 128 boys (70 normal controls, 22 boys with unilateral cryptorchidism with normal puberty, and 36 boys with delayed puberty) who had been under regular follow-up throughout puberty. All underwent a complete physical examination at intervals of 3 to 6 months, and in most a wrist X-ray was made within three months of the first ejaculation. (2) A group of 135 boys examined and questioned at their school served as additional controls. Eighty of these reported ejaculations. Despite a wide range in the chronological age at occurrence of the first conscious ejaculation, the mean bone age in all groups, including that with delayed puberty, was 13 1/2 +/- 1/2 years (SD), with a range between 12 1/2-15 1/2 years. There was no correlation between the age at first ejaculation and testicular volume, pubic hair or penis length. It is proposed that the age at the first conscious ejaculation be used as an index of maturation in male puberty.

Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty.

The aim of this study was to facilitate the distinction between the benign "mini-puberty of early infancy" and precocious puberty (PP). We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP. The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations. Their gonadotropin responses to gonadotropin releasing hormone (GnRH) test showed predominant luteinising hormone increase in 9/13. The girls presented with pubic hair development that was accompanied by breast development in 47% of cases, with low plasma estradiol concentrations. Their gonadotropin responses showed predominant follicle-stimulating hormone increase in the 17 evaluated. The patients with PP had organic central PP (5 hypothalamic hamartoma) or idiopathic central PP (n=6), or peripheral PP (one ovarian tumor and one congenital adrenal hyperplasia). The diagnosis was challenging only in 3 girls with idiopathic central PP presenting with prepubertal plasma estradiol concentrations and responses to GnRH test. The diagnosis of PP was easily determined based on the clinical presentation and the pubertal concentrations of testosterone in boys or of estradiol in girls, as was the diagnosis of central or peripheral origin of PP based on gonadotropin response to the GnRH test. Once PP is excluded, these patients need careful follow-up and physician consultation is needed if clinical pubertal signs progress.

Are pubertal changes in girls before age 8 benign?

The Lawson Wilkins Pediatric Endocrine Society recently issued new recommendations for the age at which puberty should be considered precocious, lowering the prevailing standards from 8 years to 7 years for white girls and to 6 years for black girls. The new recommendations were based on a single epidemiologic study that focused on the conditions of premature thelarche and premature adrenarche (both characterized by a single sign of puberty). Although the data were available, the authors did not comment on the low incidence of true precocious puberty (characterized by breast and pubic hair development) in their population. The hypothesis for the present study is that the new recommendations lead to underdiagnosis of endocrine pathology Using 29 International Classification of Diseases, Ninth Revision codes for diagnoses known to be associated with precocious puberty, we identified 1570 patient visits to our outpatient pediatric endocrinology clinic of white girls aged 7 to 8 and black girls aged 6 to 8 during a 5-year period Of the 1570 patient visits, 223 unique patients were identified as having been referred for the sole finding of precocious pubertal development. These 223 patients carried no other endocrine diagnoses. Eleven patients (4.9%) were found to have no true breast buds and no terminally differentiated pubic hair. A total of 105 (47.1%) of 223 patients were found to have 2 signs of puberty, consistent with true precocious puberty according to the conventional guidelines of precocity of 8 years in girls. Overall, 12.3% of patients also had diagnoses of other endocrine conditions that included congenital adrenal hyperplasia, McCune-Albright syndrome, growth hormone deficiency, hypothyroidism, hyperinsulinism, pituitary adenoma, and neurofibromatosis. A total of 35.2% of girls with true precocious puberty exhibited bone ages >3 standard deviations above the mean, indicating markedly diminished growth potential We conclude that signs of puberty in 6- to 8-year-old girls should not be considered normal or benign. Implementation of the new guidelines for the evaluation of puberty will result in failure to identify conditions that respond to early intervention.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

The growth problem is even worse in the simple virilizing forms of CAH which are detected when premature pubic hair appears in childhood, because the bone age is often several years advanced at the age of diagnosis. While a boy (or girl) with simple virilizing CAH is taller than peers at that point, he will have far fewer years remaining to grow, and may go from being a very tall 7-year-old to a 62-inch 13-year-old who has completed growth. Even with adrenal suppression, many of these children will have already had central precocious puberty triggered by the prolonged exposure of the hypothalamus to the adrenal androgens and estrogens. If this has begun, it may be advantageous to suppress puberty with a gonadotropin-releasing hormone agonist such as leuprolide to slow continuing bone maturation.

[Leydig cell tumor presenting as precocious pseudopuberty in a 4-year-old boy].

To report one case of isosexual precocious pseudopuberty in a 4-year-old boy caused by an interstitial cell testicular tumor. Physical exam, blood tests, hormonal determinations, adrenal suppression tests, bone age, orchiectomy and pathologic study of the specimen were performed. Physical examination showed a boy with muscle development, acne; body, sexual and face hair corresponding to an older boy; with increased volume of the left testicle and infantile contralateral testicle. Urinary 17-ketosteroids were elevated and did not decrease after dexametasone. Bone age corresponded to an 11-year-old standard. Pathologic study showed an interstitial cell tumor. Puberty changes disappeared after orchiectomy. This diagnosis should be taken into consideration in every case of accelerated sexual development in a boy with testicular tumor and without maturation of the contralateral testicle.

Precocious puberty in a seven-year-old boy due to human chorionic gonadotropin producing pineal tumor detected by nuclear magnetic resonance computed tomographic scanning.

We report a 7-year-old boy who developed incomplete sexual precocity due to a human chorionic gonadotropin (HCG)-producing tumor in the pineal region. The patient presented enlarged testes (3 x 2 x 2 cm) bilaterally, enlarged penis, pubic hair development of Tanner Stage III, advanced bone age and growth spurt. Initial hormonal studies showed an adult male level of testosterone (13 ng/ml) and a high level of HCG as well as HCG-beta subunit. A high basal level of LH, probably due to immuno-cross-reactivity with HCG, and low basal level of FSH, probably suppressed by testosterone, did not respond to LH-RH infusion. Search for the site of HCG production failed at the initial workup, but calcification without definite signs of tumor in the pineal region was found by conventional brain CT scan. Because of subsequent progression of clinical and laboratory findings of sexual precocity, nuclear magnetic resonance computed tomographic (NMR-CT) scan was performed, which confirmed the presence of a pineal tumor three months later. The patient was treated with 4,500 rad. of radiation therapy, and responded dramatically to this regimen. He has been followed for more than two years without any signs of recurrence. We have reported here a very rare case of incomplete sexual precocity due to an HCG-producing intracranial tumor in the pineal region. An NMR-CT scan is a very useful tool for the diagnosis of some types of pineal tumor, such as germinoma, which are highly radiosensitive.

Delayed Puberty -- Etiology -- Delayed Puberty in Males

In males, a common cause of pubertal delay is a constitutional delay of puberty and growth (CDPG). CDPG occurs when there is a decrease in the tempo of growth. The patients are generally healthy adolescent males, who appear short for age. At birth, they are an average size. However, their rate of growth slows down around 3 to 6 months of age. When they reach 3 or 4 years of age, the patients will be growing below but parallel to the 3rd percentile line. As their male peers experience puberty and a growth spurt, the patient will continue to have a lower growth velocity (2 to 4 cm/year) and pubertal delay. In normal boys, the growth spurt occurs at a testicular volume of 10 ml, which is between Tanner stage 3 and 4 (usually ages 13 to 15).  In boys with CDPG and delayed puberty, their growth spurt occurs at a later age, generally between 15 to 17 years of age. [4] When the patient finally experiences puberty, his catch-up growth will continue until he reaches his predicted target height, which may not occur until he is older than 17 or 18 years. The patient's bone age will experience delay compared to his chronological age by 2 or more years; the bone age will also correlate with his current height. [3] History will typically reveal a sibling or parent that was a "late bloomer."  For example, the father may not have experienced a growth spurt until 15 or 16 years of age. CDPG is normally a diagnosis of exclusion. However, it is often difficult to differentiate between CDPG and hypogonadotropic hypogonadism.

Clinical characteristics of 104 children referred for evaluation of precocious puberty.

There is controversy over the age of onset of puberty in normal children and the risk of missing pathology if the recently proposed revised age guidelines for referring patients are followed. However, there is little recently published information on the frequency of different diagnoses in children referred for signs of early puberty. The purposes of this study were 1) to analyze the spectrum of diagnoses made in a consecutive group of children referred to a single clinician for signs of early puberty; 2) to see whether certain patient groups were more likely to be obese; and 3) to estimate the incidence of endocrine pathology in this sample. The charts of all children referred to the author for evaluation of signs of early puberty between October 1999 and October 2002 were reviewed. Criteria were developed to assign patients to one of seven diagnostic categories based on age, growth, and clinical findings, and differences from the population mean for height and percentage of ideal body weight in the different groups were determined. Most of the patients referred (87%) were female, and the two most common diagnoses made were premature adrenarche (46%) and premature thelarche (18%). Only 9% (all girls) were thought to have true precocious puberty. Two conditions not well described in the literature, pubic hair of infancy and premature menses, were found in 8 and 5%, respectively. Patients with premature adrenarche were significantly taller and more overweight than the general population; a subgroup had evidence of accelerated growth and bone maturation but no worrisome endocrine findings. Acanthosis nigricans was found in 13% of the girls in this study, but the incidence of true endocrine pathology was very low. The majority of children being referred for precocious puberty have benign normal variants, with a very low incidence of endocrine pathology. Most girls presenting with minimal breast or pubic hair development and normal growth velocity may be managed with observation and without a full endocrine evaluation.

Peripheral Precocious Puberty -- Evaluation -- Bone age assessment

Radiographs of the hand and wrist should be performed in cases of suspected precocious puberty to assess epiphyseal maturation. An average or slightly delayed bone age  (<2 years of chronological age) suggests benign variants such as premature thelarche or premature adrenarche. On the other hand, significantly advanced bone age (>2 standard deviations above the mean for age) indicates accelerated linear growth and precocious puberty. Rapidly progressive bone age should raise concern for congenital adrenal hyperplasia or tumors originating from the ovaries, adrenal glands, or germ cells. [31]

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

Appearance of pubic hair in mid-childhood is the most common feature that leads to evaluation and diagnosis. Other accompanying features are likely to be tall stature and accelerated bone age (often 3–5 years ahead). Often present are increased muscle mass, acne, and adult body odor. In boys the penis will be enlarged. Mild clitoral enlargement may occur in girls, and sometimes a degree of prenatal virilization is recognized that may have gone unnoticed in infancy. The principal goals of treatment of nonclassical CAH are to preserve as much growth as possible and to prevent central precocious puberty if it has not already been triggered. These are more difficult challenges than in CAH detected in infancy because moderate levels of androgens will have had several years to advance bone maturation and to trigger central puberty before the disease is detected.

[Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage].

A secular trend towards a younger age of puberty onset has been reported in Chilean girls. To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Changing Etiological Trends in Male Precocious Puberty: Evaluation of 100 Cases with Central Precocious Puberty over the Last Decade.

There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic.

[Precocious pubarche: experience in 173 cases ].

Precocious pubarche (PP), defined as the development of sexual pubic hair before 8 years of age in females and before 9 years in males, is usually a benign condition but it can also be the first sign of an underlying disease. To analyze the etiology and perform a short term follow up in a cohort of patients with PP. A group of 173 patients (158 females) consulted for PP with a mean age of 7.4+/-0.1 years. These patients were followed between 15 to 60 months. Anthropometric measurements, bone age, serum levels of total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHEAS) were evaluated. Mean birth weight and length was 3024.1+/-50.5 g and 48.5+/-0.3 cm, respectively. Ten percent of children were small for gestational age at birth. Bone age was accelerated by 1.1+/-0.01 years. One hundred and twelve patients were classified as having idiopathic PP (64.7%; 105 females), 29 as central precocious puberty (16.8%; only females), 16 as exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal hyperplasia (9.2%; 11 females). PP represents a common and usually benign sign. However, 26% of cases had a pathologic underlying condition. Therefore, all children with PP should be evaluated by a pediatric endocrinologist. Low birth weight was not frequent in this cohort and these patients did not show EA .

Pubarche

Pubarche refers to the first appearance of pubic hair at puberty. Pubarche is one of the physical changes of puberty and can occur independently of complete puberty. Pubarche usually results from rising levels of androgen and not estrogens in females, and androgens in males from the adrenal glands, ovaries, or testes but may also result from exposure to an anabolic steroid. When pubarche occurs prematurely (in early or mid-childhood), it is referred to as premature pubarche or precocious puberty and may warrant an evaluation. Premature adrenarche is the most common cause of premature pubarche. Early occurrences can arise due to congenital adrenal hyperplasia, androgen-producing tumors of the adrenals or gonads. When adrenarche, central puberty, and all pathologic conditions have been excluded, the term isolated premature pubarche is used to describe the unexplained development of pubic hair at an early age without other hormonal or physical changes of puberty. Average age

Ussefulnes of imaging techniques in the diagnostics of precocious puberty in boys.

Precocious puberty (PP) is defined as the appearance of symptoms of puberty in girls before 8 years of age and in boys under 9. Statistically, it occurs much more frequently in girls, while it is a rare pathology in boys. Over the period of 10 years, between 1999 and 2009, 39 girls and 17 boys aged 18 months - 9 years were diagnosed with precocious puberty,, and treated at the Endocrinology Clinic. THE FOLLOWING TESTS WERE PERFORMED IN ALL CHILDREN: physical and anthropometric examinations, abdominal ultrasound scan (US) with evaluation of adrenal glands, examination of testes in boys or breasts and pelvic organs in girls, evaluation of skeletal age and, in selected cases, CT scans of the abdomen, MRI of the CNS, and hormonal laboratory tests. In the group of 17 boys the findings included: gonadotropin -dependent central puberty in 6 boys: idiopathic in 5 cases, and 1 case of a brain tumor - astrocytoma. Gonadotropin-independent precocious pseudopuberty was diagnosed in 11 boys: congenital adrenal hyperplasia in 5; in 1case - hyperandrogenism caused by overactivity of 5-α reductase; in 2 subjects - adrenal adenoma; in 2 boys adrenocortical carcinoma was diagnosed and Leydig cell tumor of testis in 1. 1. Precocious puberty occurs less often in boys, but in our population it was found in 17 boys of 56 treated children, which constituted as much as 30%. 2. Precocious pseudopuberty was found in 64% of the boys with PP. 3. Adrenal and testicular tumors were the causes of precocious puberty in the youngest group of boys aged 18 months - 6 years.

Puberty

Testicular size In boys, testicular enlargement is the first physical manifestation of puberty (and is termed gonadarche). Testes in prepubertal boys change little in size from about 1 year of age to the onset of puberty, averaging about 2–3 cm in length and about 1.5–2 cm in width. The size of the testicles is among the parameters of the Tanner scale for male genitals, from stage I which represents a volume of less than 1.5 ml, to stage V which represents a testicular volume of greater than 20 ml. Testicular size reaches maximal adult size about 6 years after the onset of puberty. While 18–20 cm3 is an average adult size, there is wide variation in testicular size in the normal population. After the boy's testicles have enlarged and developed for about one year, the length and then the breadth of the shaft of the penis will increase and the glans penis and corpora cavernosa will also start to enlarge to adult proportions. Male musculature and body shape

Pediatric gynaecology

Precocious puberty occurs when children younger than 8 experience changes indicative of puberty, including development of breast buds (thelarche), pubic hair, and a growth spurt. Thelarche before 8 is considered abnormal. Though not all precocious puberty has a specific pathological cause, it may indicate a serious medical problem and is thoroughly evaluated. In most cases, the cause of precocious puberty cannot be identified. "Central precocious puberty" or "true precocious puberty" stems from early activation of the hypothalamic-pituitary-ovarian axis. It occurs in 1 in 5,000 to 1 in 10,000 people and can be caused by a lesion in the central nervous system or have no apparent cause. "Peripheral precocious puberty" or "GnRH independent precocious puberty" does not involve the hypothalamic-pituitary-ovarian axis, instead, it involves other sources of hormones. The causes of peripheral precocious puberty include adrenal or ovarian tumors, congenital adrenal hyperplasia, and exogenous

Precocious Puberty -- Differential Diagnosis

Precocious puberty requires differentiation from the benign forms of puberty. [8] These include Premature Thelarche: It is the premature unilateral or bilateral development of the breast tissue in girls between the age of 12 to 24 months. There are no other associated pubertal changes. Bone age, growth velocity, and biochemical testing are normal. It is usually a diagnosis of exclusion. Frequent clinical follow up to monitor growth, and pubertal progression is required. Premature Adrenarche: The early production of adrenal androgens characterizes this benign condition. It presents with pubic or axillary hair, body odor, or acne before the age of 8 years.  There is no breast development in females and no testicular enlargement in males. Bone age is usually not advanced. It is essential to rule out exposure to androgen sources such as creams or gels, adrenal tumors, and late-onset CAH.

First_Aid_Step2

Peripheral precocious puberty: Also called pseudo-precocious puberty. Results from nonhypothalamic GnRH production. Signs of estrogen excess (breast development and possibly vaginal bleeding) point to ovarian cysts or tumors. Signs of androgen excess (pubic and/or axillary hair, enlarged clitoris, acne, and/or ↑ body odor) suggest adrenal tumors or congenital adrenal hyperplasia (CAH). First step: Obtain a radiograph of the wrist and hand to determine bone age. If bone age is within one year of chronological age, puberty has not started or has just recently begun. If bone age exceeds chronological age by > 2 years, puberty has been present for at least one year or is progressing rapidly. Next step: Conduct a GnRH agonist (leuprolide) stimulation test. Central precocious puberty: If LH response is , obtain a cranial MRI to look for CNS tumors. In girls 6–8 years of age with signs of precocious puberty, the incidence of CNS tumor is 2% in the absence of other CNS signs.

Precocious puberty

Adrenocortical oncocytomas are rare with mostly benign and nonfunctioning tumors. There have been only three cases of functioning adrenocortical oncocytoma that have been reported up until 2013. Children with adrenocortical oncocytomas will present with "premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone" which are some of the presentations associated with precocious puberty. Precocious puberty in girls begins before the age of 8. The youngest mother on record is Lina Medina, who gave birth at the age of either 5 years, 7 months and 17 days or 6 years 5 months as mentioned in another report. "Central precocious puberty (CPP) was reported in some patients with suprasellar arachnoid cysts (SAC), and SCFE (slipped capital femoral epiphysis) occurs in patients with CPP because of rapid growth and changes of growth hormone secretion." If no cause can be identified, it is considered idiopathic or constitutional.

Medical uses of bicalutamide

In the trial, growth velocity was decreased, bone age advancement was slowed, aggressiveness was decreased, and masculinization, measured via Tanner staging of pubic hair and genitals, did not appear to further progress. However, the decrease in growth rate was modest and fell just short of reaching statistical significance (p = 0.053). Conversely, although the decrease in rate of bone maturation was described as modest similarly, the ratio of bone age to chronological age was significantly reduced (p < 0.0001). Linear growth and skeletal maturation during normal puberty is mainly due to estradiol and not testosterone in both boys and girls, and hence inhibition of these processes with the combination of bicalutamide and anastrozole in precocious puberty would in theory be mostly dependent on the aromatase inhibitor rather than on bicalutamide. Testicular volume increased mildly over the year that the boys were observed. A New Drug Application of bicalutamide for in the United

Virilization

Normal virilization In common as well as medical usage, virilization often refers to the process of normal male puberty. These effects include growth of the penis and testes, accelerated growth, development of pubic hair, and other androgenic hair of face, torso, and limbs, deepening of the voice, increased musculature, thickening of the jaw, prominence of the neck cartilage, and broadening of the shoulders. Abnormal childhood virilization Virilization can occur in childhood in both males and females due to excessive amounts of androgens. Typical effects of virilization in children are pubic hair, accelerated growth and bone maturation, increased muscle strength, acne, and adult body odor. In males, virilization may signal precocious puberty, while congenital adrenal hyperplasia and androgen producing tumors (usually) of the gonads or adrenals are occasional causes in both sexes.

Thelarche

Precocious puberty Precocious puberty is a condition where children undergo puberty before the age of seven or eight years. Precocious puberty differs from premature thelarche in that the individual experiences additional aspects of puberty including menarche, adrenarche, pubarche, vaginal discharge, and bone growth, while premature thelarche is identified by the sole presence of early thelarche. Though premature thelarche and precocious puberty are distinct conditions, there is some overlap; an estimated 14 to 18 percent of females who exhibit premature thelarche will additionally develop precocious puberty. Precocious puberty can be identified using a pelvic ultrasound to assess the size of ovaries and uterus relative to the individual's age. Other methods of diagnosis consist of blood tests to determine hormone levels and simple physician assessments with follow-up appointments to track the progression of development.

Human penis

Growth in puberty On entering puberty, the penis, scrotum and testicles will enlarge toward maturity. During the process, pubic hair grows above and around the penis. A large-scale study assessing penis size in thousands of 17- to 19-year-old males found no difference in average penis size between 17-year-olds and 19-year-olds. From this, it can be concluded that penile growth is typically complete not later than age 17, and possibly earlier. Physiological functions Urination

Precocious puberty

Diagnosis Studies indicate that breast development in girls and the appearance of pubic hair in both girls and boys are starting earlier than in previous generations. As a result, "early puberty" in children as young as 9 and 10 is no longer considered abnormal, particularly with girls. Although it is not considered as abnormal, it may be upsetting to parents and can be harmful to children who mature physically at a time when they are immature mentally. No age reliably separates normal from abnormal processes in children, but the following age thresholds for evaluation are thought to minimize the risk of missing a significant medical problem: Breast development in boys before appearance of pubic hair or testicular enlargement Pubic hair or genital enlargement (gonadarche) in boys with onset before 9.5 years Pubic hair (pubarche) before 8 or breast development (thelarche) in girls with onset before 7 years Menstruation (menarche) in girls before 10 years

Puberty

Puberty onset Puberty is preceded by adrenarche, marking an increase of adrenal androgen production between ages 6–10. Adrenarche is sometimes accompanied by the early appearance of axillary and pubic hair. The first androgenic hair resulting from adrenarche can be also transient and disappear before the onset of true puberty. The onset of puberty is associated with high GnRH pulsing, which precedes the rise in sex hormones, LH and FSH. Exogenous GnRH pulses cause the onset of puberty. Brain tumors which increase GnRH output may also lead to premature puberty.