Question always involves the brainstem. We have a right hemiparesis and involvement of the left facial nucleus, since it has affected the upper and lower facial; therefore we have a crossed clinical picture, having to think about brainstem involvement. If we have in a quick diagram where the nuclei of the cranial pairs start from: the first 4 above the pons, the next 4 in the pons, and the last 4 below the pons, we have that the facial nucleus is in the middle 4. That is, left facial nucleus, left pons, so answer 4.

Question always involves the brainstem. We have a right hemiparesis and involvement of the left facial nucleus, since it has affected the upper and lower facial; therefore we have a crossed clinical picture, having to think about brainstem involvement. If we have in a quick diagram where the nuclei of the cranial pairs start from: the first 4 above the pons, the next 4 in the pons, and the last 4 below the pons, we have that the facial nucleus is in the middle 4. That is, left facial nucleus, left pons, so answer [HIDDEN].

An individual presents with "muscle weakness" (spastic hemiparesis) of both right extremities, with hyperreflexia and Babinski's sign, along with a "facial flaccid paralysis" of the left hemiface, with inability to close the left eye or retract the left side of the mouth, in addition to other alterations. From the data described, it is an alteration that affects, among other elements, the motor fascicles: cortico-spinal and cortico-nuclear, but at what level of the neuroaxis would the lesion be located?

At the level of the area 4 of Brodmann of the cerebral cortex of the right side.

In the internal capsule, posterior arm on the right side.

In the medial portion of the caudal protuberance of the left side.

In the medulla oblongata before decussation of the right cortico-spinal fascicle.

Facial motor nucleus

The neurons in the dorsal aspect of the facial motor nucleus receive inputs from both sides of the cortex, while those in the ventral aspect mainly receive contralateral inputs (i.e. from the opposite side of the cortex). The result is that both sides of the brain control the muscles of the upper face, while the right side of the brain controls the lower left side of the face, and the left side of the brain controls the lower right side of the face. Clinical significance As a result of the corticobulbar input to the facial motor nucleus, an upper motor neuron lesion to fibers innervating the facial motor nucleus results in central seven. The syndrome is characterized by spastic paralysis of the contralateral lower face. For example, a left corticobulbar lesion results in paralysis of the muscles that control the lower right quadrant of the face.

Facial motor nucleus

Branches of the facial nerve leaving the facial motor nucleus (FMN) for the muscles do so via both left and right posterior (dorsal) and anterior (ventral) routes. In other words, this means lower motor neurons of the facial nerve can leave either from the left anterior, left posterior, right anterior or right posterior facial motor nucleus. The temporal branch travels out from the left and right posterior components. The inferior four branches do so via the left and right anterior components. The left and right branches supply their respective sides of the face (ipsilateral innervation). Accordingly, the posterior components receive motor input from both hemispheres of the cerebral cortex (bilaterally), whereas the anterior components receive strictly contralateral input. This means that the temporal branch of the facial nerve receives motor input from both hemispheres of the cerebral cortex whereas the zygomatic, buccal, mandibular and cervical branches receive information

Facial motor nucleus

A lesion on either the left or right side would affect both the anterior and posterior routes on that side because of their close physical proximity to one another. So, a lesion on the left side would inhibit muscle innervation from both the left posterior and anterior routes, thus paralyzing the whole left side of the face (Bell’s palsy). With this type of lesion, the bilateral and contralateral inputs of the posterior and anterior routes, respectively, become irrelevant because the lesion is below the level of the medulla and the facial motor nucleus. Whereas at a level above the medulla a lesion occurring in one hemisphere would mean that the other hemisphere could still sufficiently innervate the posterior facial motor nucleus, a lesion affecting a lower motor neuron would eliminate innervation altogether because the nerves no longer have a means to receive compensatory contralateral input at a downstream decussation.

How to Localize Neurologic Lesions by Physical Examination -- Clinical Significance

Hemiplegia can result from a unilateral lesion of the brain stem, internal capsule, or cerebral cortex. Brain stem lesions result in crossed hemiplegia. For example, a left pontine lesion will result in left facial weakness of lower motor neuron type and right-sided hemiplegia. Similarly, a lesion in the left midbrain will result in left-sided oculomotor weakness with right hemiparesis and right facial weakness of upper motor neuron type. This constellation of signs is called Weber syndrome. Lesions above the level of the brainstem result in uncrossed hemiplegia. For example, a lesion in the left internal capsule would result in right hemiplegia and right facial weakness of the upper motor neuron type. A left cortical lesion may also result in cortical dysfunction in addition to right hemiparesis and facial weakness of upper motor neuron type. [5] [6] [7]

Contralateral Tongue Deviation Due to Paramedian Pontine Infarction: A Brief Review of Cortico-Hypoglossal Projections.

BACKGROUND Motor function of the tongue is controlled by the hypoglossal nucleus (the lower motor neuron) and its supranuclear innervation (the upper motor neuron). Tongue deviation due to muscle weakness on one side is common in brain stem stroke and is usually associated with dysarthria and dysphagia that decrease the patient's quality of life. This case report presents a typical but rarely discussed case of tongue deviation secondary to a brain stem stroke. In addition, it also offers a concise review of both the ipsilateral and the contralateral cortico-hypoglossal fibers that innervate the hypoglossal nucleus. Even though the direction of the tongue deviation offers essential clues to localizing the brain lesion, many providers lack experience and knowledge in this area. CASE REPORT We report the case of an 81-year-old right-handed male patient with right-sided hemiparesis, right lower facial droop, dysarthria, and tongue deviated to the right side without fasciculation or atrophy. The Babinski sign was positive on the right. Magnetic resonance imaging revealed an infarct in the left paramedian pontine. Since both the tongue deviation and the hemiparesis were right-sided, contralateral to the side of the lesion, we concluded that the lesion affected the cortico-hypoglossal fibers and the corticospinal fibers prior to their decussations. CONCLUSIONS The case report reviews the projections of the corticospinal fibers. Each hypoglossal nucleus receives input from both hemispheres, with the contralateral descending fibers passing through the medial part of the ventral pons and the ipsilateral descending fibers passing through the more lateral aspect of the pons. The decussation is generally located at the pontomedullary junction, with exceptions due to individual variance.

[A case report of Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral thalamomesencephalic lesion].

We report a rare case showing Weber's syndrome associated with supranuclear vertical gaze palsy caused by the ipsilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), which is regarded as the supranuclear control center of vertical gaze. To date, no literature concerning Weber's syndrome associated with the ipsilateral riMLF lesion was documented. The patient was a 53-year-old female, who suddenly developed unconsciousness and left-sided weakness. Neurological findings on admission revealed right third nerve palsy, severe supranuclear vertical gaze palsy, almost complete convergence palsy, left hemiparesis and hyperreflexia with positive Babinski's sign on the left side. There was no sign of pupillary disturbance or no abnormality of the horizontal movements of the left eye. The vestibulo-ocular reflex of the left eye was preserved. There was no sensory disturbance. Cranial MRI had the advantages in demonstrating unilateral ischemic lesions at the cerebral peduncle and the thalamomesencephalic junction involving the unilateral riMLF on the right side. Recent reports have demonstrated that supranuclear vertical gaze palsy is caused by the unilateral riMLF lesion. We confirm that the unilateral riMLF lesion causes supranuclear vertical gaze palsy in our case and that cranial MRI has the advantages in demonstrating the specific lesion.

[Case of suspected multiple sclerosis with transcallosal lesions involving the upper surface of the corpus callosum].

A 26-year-old woman noticed gradually progressive, right lower leg weakness over a 1.5-month period. Neurological examination revealed right hemiparesis with slightly increased deep tendon reflexes, Babinski's sign on the right side, loss of position sense in the right leg, and slight loss of superficial sensation in the right toes. MR FLAIR images showed a high intensity area measuring 5 x 2 x 3 cm in the left frontal lobe, extending to the outer surface of the body of the corpus callosum and the adjacent right cingulate gyrus. Gadolinium enhancement was seen along the cortex and the outer surface of the body of the corpus callosum. CSF findings showed no pleocytosis, a protein content of 32 mg/dl, a sugar level of 85 mg/dl, and an IgG index of 0.46. The biopsy specimen obtained from the superior frontal gyrus showed perivascular cuffing of T-lymphocytes and some B-lymphocytes, as well as multiple small foci of demyelination. Starting on the second day of admission, the patient was treated with methylprednisolone pulse therapy (1,000 mg/day for 3 days); she was then switched to oral prednisolone (20 mg/day). Thereafter, the patient had two clinical relapses: one was due to a lesion in the dorsal part of the medulla oblongata associated with a disturbance of deep sensation in both hands, and the other was due to a lesion involving the right internal capsule, the globus pallidus, and the caudate nucleus associated with left facial nerve palsy. Visual evoked potentials suggested a demyelinating lesion in the right optic nerve. We suspected a diagnosis of multiple sclerosis based on the presence of more than two clinical episodes of neurological deficits with identifiable lesions on MRI. Multiple sclerosis should be considered in the differential diagnosis of lesions located in the outer part of the corpus callosum and transcallosal bilateral hemispheres on MRI, even though inner callosal lesions are common in multiple sclerosis.

Facial motor nucleus

Now, because the anterior FMN receives only contralateral cortical input whereas the posterior receives that which is bilateral, a corticobulbar lesion (UMN lesion) occurring in the left hemisphere would eliminate motor input to the right anterior FMN component, thus removing signaling to the inferior four facial nerve branches, thereby paralyzing the right mid- and lower-face. The posterior component, however, although now only receiving input from the right hemisphere, is still able to allow the temporal branch to sufficiently innervate the entire forehead. This means that the forehead will not be paralyzed. The same mechanism applies for an upper motor neuron lesion in the right hemisphere. The left anterior FMN component no longer receives cortical motor input due to its strict contralateral innervation, whereas the posterior component is still sufficiently supplied by the left hemisphere. The result is paralysis of the left mid- and lower-face with an unaffected forehead.

Neuroanatomy, Facial Colliculus -- Clinical Significance -- Lateral Gaze Palsy

A lesion located in the abducens nucleus will lead to the paralysis of the ipsilateral lateral rectus. Although the function of the contralateral medial rectus muscle, which is innervated by CN III, will remain intact, interneurons projecting from the damaged CN VI nucleus will no longer be able to send proper signals through the contralateral MLF to the CN III nucleus. As a result, horizontal eye movements are unable to coordinate when both eyes attempt to gaze towards the side of the lesion. For example, if the right nucleus of CN VI is damaged, the right CN VI fibers projecting to the right lateral rectus muscle will be impaired. Since the left CN III nucleus and its nerves are not damaged, there will be no problem contracting the left medial rectus muscle when CN III is activated, and there is no involvement of CN VI. In this example, the lesion of the right nucleus of CN VI impairs the left MLF that projects to the left CN III nucleus, and thus the left CN III nerve cannot stimulate the contraction of the left medial rectus muscle. Ultimately, horizontal eye movements will become disrupted, and both eyes will look straight ahead when instructing the patient to turn their gaze to the right. The patient will have no problem gazing to the left.

Internal capsule

Posterior limb The posterior limb of internal capsule (or occipital part) is the portion of the internal capsule posterior to the genu. The anterior two-thirds of the occipital part of the internal capsule contains fibers of the corticospinal tract, which arise in the motor area of the cerebral cortex and, passing downward through the middle three-fifths of the base of the cerebral peduncle, are continued into the pyramids of the medulla oblongata. The posterior third of the occipital part contains: sensory fibers, largely derived from the thalamus, though some may be continued upward from the medial lemniscus the fibers of optic radiation, from the lower visual centers to the cortex of the occipital lobe; acoustic fibers, from the lateral lemniscus to the temporal lobe fibers that pass from the occipital and temporal lobes to the pontine nuclei

InternalMed_Harrison

Superior cerebellar peduncle Midpontine syndrome: Medial longitudinal fasciculus 5th n. sensory nucleus 5th n. motor nucleus Spinothalamic Medial lemniscus FIGURE 446-12 Axial section at the level of the midpons, depicted schematically on the left, with a corresponding magnetic resonance image on the right. Approximate regions involved in medial and lateral midpontine stroke syndromes are shown. Signs and symptoms: Structures involved 1. Medial midpontine syndrome (paramedian branch of midbasilar artery) On side of lesion Ataxia of limbs and gait (more prominent in bilateral involvement): Pontine nuclei On side opposite lesion Paralysis of face, arm, and leg: Corticobulbar and corticospinal tract Variable impaired touch and proprioception when lesion extends posteriorly: Medial lemniscus 2.

Precentral gyrus

Blood supply Branches of the middle cerebral artery provide most of the arterial blood supply for the primary motor cortex. The medial aspect (leg areas) is supplied by branches of the anterior cerebral artery. Clinical significance Lesions of the precentral gyrus result in paralysis of the contralateral side of the body (facial palsy, arm-/leg monoparesis, hemiparesis) - see upper motor neuron. New research has identified this as the part of the brain that makes sure our words are being properly articulated. This knowledge could help treat speech disorders and neural disorders in the future, the researchers say. Additional images See also Corticospinal tract Motor cortex List of regions in the human brain References Gyri Frontal lobe

[Left lateral gaze paresis due to subcortical hematoma in the right precentral gyrus].

We report a case of transient left lateral gaze paresis due to a hemorrhagic lesion restricted in the right precentral gyrus. A 74-year-old female experienced a sudden clumsiness of the left upper extremity. A neurological examination revealed a left central facial paresis, distal dominant muscle weakness in the left upper limb and left lateral gaze paresis. There were no other focal neurological signs. Laboratory data were all normal. Brain CTs and MRIs demonstrated a subcortical hematoma in the right precentral gyrus. The neurological symptoms and signs disappeared over seven days. A recent physiological study suggested that the human frontal eye field (FEF) is located in the posterior part of the middle frontal gyrus (Brodmann's area 8) and the precentral gyrus around the precentral sulcus. More recent studies stressed the role of the precentral sulcus and the precentral gyrus. Our case supports those physiological findings. The hematoma affected both the FEF and its underlying white matter in our case. We assume the lateral gaze paresis is attributable to the disruption of the fibers from the FEF. It is likely that fibers for motor control of the face, upper extremity, and lateral gaze lie adjacently in the subcortical area.

Internal capsule

Lesions of the genu of the internal capsule affect fibers of the corticobulbar tract. The primary motor cortex sends its axons through the posterior limb of the internal capsule. Lesions, therefore, result in a contralateral hemiparesis or hemiplegia. While symptoms of weakness due to an isolated lesion of the posterior limb can initially be severe, recovery of motor function is sometimes possible due to spinal projections of premotor cortical regions that are contained more rostrally in the internal capsule. References External links Rostral basal ganglia and associated structures

Pyramidal tracts

Corticobulbar tract Fibres from the ventral motor cortex travel with the corticospinal tract through the internal capsule, but terminate in a number of locations in the midbrain (cortico-mesencephalic tract), pons (Corticopontine tract), and medulla oblongata (cortico-bulbar tract). The upper motor neurons of the corticobulbar tract synapse with interneurons or directly with the lower motor neurons located in the motor cranial nerve nuclei, namely oculomotor, trochlear, motor nucleus of the trigeminal nerve, abducens, facial nerve and accessory and in the nucleus ambiguus to the hypoglossal, vagus and accessory nerves. These nuclei are supplied by nerves from both sides of the brain, with the exception of the parts of the facial nerve that control muscles of the lower face. These muscles are only innervated by nerves from the contralateral (opposite) side of the cortex.

InternalMed_Harrison

Hemiparesis Hemiparesis results from an upper motor neuron lesion above the midcervical spinal cord; most such lesions are above the foramen magnum. The presence of other neurologic deficits helps localize the lesion. Thus, language disorders, for example, point to a cortical lesion. Homonymous visual field defects reflect either a cortical or a subcortical hemispheric lesion. A “pure motor” hemiparesis of the face, arm, and leg often is due to a small, discrete lesion in the posterior limb of the internal capsule, cerebral peduncle, or upper pons. Some brainstem lesions produce “crossed paralyses,” consisting of ipsilateral cranial nerve signs and contralateral hemiparesis (Chap. 446). The absence of cranial nerve signs or facial weakness suggests that a hemiparesis is due to a lesion in the high cervical spinal cord, especially if associated with the Brown-Séquard syndrome (Chap. 456).

Primary motor cortex

Clinical significance Lesions of the precentral gyrus result in paralysis of the contralateral side of the body (facial palsy, arm-/leg monoparesis, hemiparesis) - see upper motor neuron. Movement coding Evarts suggested that each neuron in the motor cortex contributes to the force in a muscle. As the neuron becomes active, it sends a signal to the spinal cord, the signal is relayed to a motorneuron, the motorneuron sends a signal to a muscle, and the muscle contracts. The more activity in the motor cortex neuron, the more muscle force.

Neurology_Adams

Zee DS, Hain TC, Carl JR: Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol 21:383, 1987. Figure 13-1. The supranuclear pathways subserving horizontal gaze to the left. The pathway originates in the right frontal cortex, descends in the internal capsule, decussates at the level of the rostral pons, and descends to synapse in the left pontine paramedian reticular formation (PPRF). Further connections with the ipsilateral sixth nerve nucleus and contralateral medial longitudinal fasciculus are also indicated. The right MLF (green line) is labeled between the abducens and oculomotor nuclei and the vestibular nuclei (VN) are shown on the right. LR, lateral rectus; MLF, medial longitudinal fasciculus; MR, medial rectus.

Neuroanatomy, Upper Motor Neuron Lesion -- Structure and Function

Knowledge about the pathways of the pyramidal tracts is paramount to understanding the clinical presentation of UMN lesions. Lesions above or below the pyramidal decussation will have symptoms on different parts of the body. UMN lesions rostral to the pyramidal decussation will result in symptoms contralateral to the site of the lesion. For example, a unilateral lesion on the right corticospinal tract before the pyramidal decussation would cause weakness and spasticity of musculature on the left side of the body.  UMN lesions caudal to the decussation will cause symptoms ipsilateral to the site of the lesion. This presentation would generally be with lesions to the spinal cord. For example, left-sided lesions of the corticospinal tract in the spinal cord will cause left-sided weakness and spasticity. Unilateral UMN lesions innervating cranial nerves do not manifest with clinically significant symptoms due to their bilateral innervation from the left and right motor areas. Hence, only bilateral lesions to the UMN of cranial nerves would create deficits. Lesions of UMN’s to CN VII and XII are the exceptions because of their unilateral innervation from contralateral motor areas. For example, a right-sided UMN lesion to the motor area that controls CN VII would manifest as a weakness on the left lower face. [5]

How to Localize Neurologic Lesions by Physical Examination -- Function

Descending fibers of the corticospinal tract travel from the cerebral cortex to corona radiata, posterior limb of the internal capsule, cerebral peduncles, pons, and medulla. At the lower part of the medulla, most of these fibers cross the midline, continue as the lateral corticospinal tract and descend through the white matter of the cord to innervate the anterior horn cells. This crossing over of corticospinal tract fibers is called pyramidal decussation.  Resultantly, pyramidal cells of the right cerebral cortex innervate left spinal motor nuclei and vice versa. Spinal motor nuclei innervating skeletal muscles of upper and lower limbs receive upper motor neuron innervation only from the contralateral side. Lower motor neurons of cranial nerves, on the other hand, are innervated by corticobulbar fibers from both sides. Therefore despite damage to corticobulbar fibers on one side, cranial motor nuclei will continue to receive upper motor supply from the other side. The nucleus of the facial nerve, however, can be considered a hybrid. Like other cranial motor nuclei, the upper half of the facial nucleus receives bilateral upper motor neuron innervation. On the other hand, the lower half receives innervation only from the contralateral side.

Alternating hemiplegia

Symptoms and signs Superior alternating hemiplegia Superior alternating hemiplegia (also known as Weber syndrome) has a few distinct symptoms: contralateral hemiparesis of limb and facial muscle accompanied by weakness in one or more muscles that control eye movement on the same side. Another symptom that appears is the loss of eye movement due to damage to the oculomotor nerve fibers. The upper and lower extremities have increased weakness. Middle alternating hemiplegia Middle alternating hemiplegia (also known as Foville Syndrome) typically constitutes weakness of the extremities accompanied by paralysis of the extraocular muscle specifically lateral rectus, on the opposite side of the affected extremities, which indicates a lesion in the caudal and medial pons involving the abducens nerve root (controls movement of the eye) and corticospinal fibers (carries motor commands from the brain to the spinal cord).

The corticobulbar tract fibers originate from the parts of the motor cortex that represent the face. The axons share a similar trajectory to the corticospinal tract descending through the corona radiata and the internal capsule. At the level of the brainstem, the axons will synapse with each cranial nerve nuclei at their respective levels. The upper motor neuron innervation of most cranial nerves is bilateral which means that each cranial nerve receives impulses from the left and right hemisphere. This bilateral innervation pertains to the muscles of the eyes, jaw, pharynx, upper face, larynx, and neck. Two exceptions to this rule are CN VII and XII. The control of tongue protrusion by CN XII and the control of the muscles of the lower face by CN VII only receive contralateral innervation from the pyramidal tract. [4]

InternalMed_Harrison

On side opposite lesion Paralysis of face, arm, and leg: Corticobulbar and corticospinal tract Variable impaired touch and proprioception when lesion extends posteriorly: Medial lemniscus 2. On side of lesion Ataxia of limbs: Middle cerebellar peduncle Paralysis of muscles of mastication: Motor fibers or nucleus of fifth nerve Impaired sensation over side of face: Sensory fibers or nucleus of fifth nerve On side opposite lesion Impaired pain and thermal sense on limbs and trunk: Spinothalamic tract the lateral two-thirds of the pons and middle and superior cerebellar peduncles; and (3) bilateral long circumferential (superior cerebellar and anterior inferior cerebellar arteries), which course around the pons to supply the cerebellar hemispheres.

[Analysis of hemiparesis with homolateral ataxia by single photon emission CT].

Case 1. A 46-year-old man suddenly developed mild gait disturbance and left hemiparesis. On examination, gross strength was slightly reduced in the left extremities. The finger-to-nose and heel-to-knee tests disclosed moderate dyssynergia and dysmetria on the left side that could not be explained by the muscular weakness. Deep tendon reflexes were more brisk in the left extremities. There was no Babinski sign. Magnetic resonance imaging showed a region of high signal intensity in the right posterior limb of internal capsule with extension into lateral thalamus. The lesion involved the cortico-ponto-cerebellar pathway and partly the dentato-rubro-thalamo-cortical pathway. No lesions were seen in the brainstem. Single photon emission CT with 123I-IMP showed left cerebellar hypoperfusion termed crossed cerebellar diaschisis by Baron et al. Case 2. A 65-year-old female developed weakness of the left extremities and gait disturbance. On examination, there was a horizontal nystagmus on lateral gaze to each side. She showed dysarthria, mild left hemiparesis and slight left hypesthesia. The finger-nose and heel-knees tests revealed moderate dysmetria and dyssynergia on the left side. Deep tendon reflexes were hyperactive in the left extremities with left Babinski sign. CT showed a low density area in the right basis pontis at about middle level. Intravenous digital subtraction angiography revealed a slight stenosis of right vertebral artery, but no other abnormality. The lesion involved the cortico-ponto-cerebellar pathway. Single photon emission CT with 123I-IMP showed left cerebellar hypoperfusion. The right cerebellar blood flow was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution and course of cortico-respiratory projections for voluntary activation in man. A transcranial magnetic stimulation study in healthy subjects and patients with cerebral ischemia.

The function and course of the cortico-respiratory projections in man are not yet well established. In 30 normal volunteers respiratory muscles were activated by magnetic stimulation of the motor cortex and the cervical and thoracic spinal roots with bilateral recordings from the respiratory muscles. Following cortical stimulation contralateral responses were obtained in all subjects during voluntary inspiration showing a mean latency and amplitude of 13.4+/-1.4ms/1.6+/-1.2 mV (stimulation of the left hemisphere) and 13.2+/-1.3ms/2.5+/-2.5 mV (stimulation of the right hemisphere). Ipsilateral responses were obtained in only 18 (right side) and 21 (left side) subjects and had a significantly (p < 0.001) longer mean latency and lower mean amplitude than the contralateral responses. In 31 patients with impairment of the cortico-respiratory projections due to cerebral infarction demonstrated by magnetic resonance imaging studies, the responsible lesion topography was analysed. We found that, 1. the voluntary activation of respiratory muscles is mediated predominantly by the contralateral motor cortex, 2. the descending cortico-respiratory projections are located within the pyramidal tract, and 3. the cortico-respiratory projections to the respiratory muscles are frequently affected in patients with hemiparesis due to acute stroke. These findings might explain the increased incidence of pneumonia at the hemiparetic side in patients with cerebral ischemia as shown in previous studies.

Corticospinal Tract Lesion -- Introduction

The corticospinal tract controls primary motor activity for the somatic motor system from the neck to the feet. It is the major spinal pathway involved in voluntary movements. The tract begins in the primary motor cortex, where the soma of pyramidal neurons are located within cortical layer V. Axons for these neurons travel in bundles through the internal capsule, cerebral peduncles, and ventral pons. They stay in the ventral position within the medulla as the pyramids. A majority of the axons cross the midline at the pyramidal decussation between the brainstem and spinal cord to form the lateral corticospinal tract (Figure 1A). This crossover causes the left side of the brain to control the right side of the spinal cord and the right side of the brain to control the left side of the spinal cord. A small number of axons remain on the ipsilateral side to form the anterior corticospinal tract. Axons of both anterior and lateral corticospinal tracts move into the gray matter of the ventral horn to synapse onto lower motor neurons. These lower motor neurons exit the spinal cord to contract muscle. [1] While the anterior corticospinal tract assists with axial muscle motor control, the lateral corticospinal tract is the primary pathway for motor information to the body. Injuries to the lateral corticospinal tract results in ipsilateral paralysis (inability to move), paresis (decreased motor strength), and hypertonia (increased tone) for muscles innervated caudal to the level of injury. [2] The lateral corticospinal tract can suffer damage in a variety of ways. The most common types of injury are central cord syndrome, Brown-Sequard syndrome, and anterior spinal cord syndrome.

Neurology_Adams

Distinguishing capsular from pontine hemiplegia It is often not possible to distinguish a hemiplegia of pontine origin from one of deep cerebral origin unless there is an associated cranial nerve palsy to triangulate the lesion to a specific part of the brainstem. In both, the face, arm, hand, leg, and foot are affected because of the location of the descending motor fibers into a small segmental region in both structures. With brainstem lesions, as with cerebral ones, a flaccid paralysis gives way to spasticity after a few days or weeks, and there is no satisfactory explanation for the occurrence in some cases of spasticity from the onset of the stroke. There is also may be a combined hemiparesis and ataxia of the limbs on the same side. With a hemiplegia of pontine origin, however, the eyes may deviate to the side of the paralysis, that is, the opposite of what occurs with supratentorial lesions. The pattern of sensory disturbance may also be helpful. A dissociated sensory deficit

Structure-function relationships in rat brain stem subnucleus interpolaris. VIII. Cortical inputs.

1. Spinal trigeminal (SpV) subnucleus interpolaris (SpVi) receives inputs from trigeminal (V) first- and second-order neurons, monoamine-containing brain stem nuclei, and somatosensory cortex. Prior studies suggest that SpVi receptive-field (RF) properties cannot be predicted solely on the basis of primary afferent inputs. To assess the cortico-V projection and its role in SpVi RFs, anatomic and electrophysiological experiments were conducted. 2. Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat-germ-agglutinized horseradish peroxidase (WGA-HRP) were used as anterograde tracers to study cortico-V axons in 24 normal adult rats. Injections into SI barrel cortex-labeled pyramidal fibers that decussated at all levels of the V brain stem complex, though crossing fibers were most numerous in the pyramidal decussation and pons. A small number of axons projected to ipsilateral V brain stem subnuclei. PHA-L-labeled pyramidal fibers did not give rise to collaterals in their descent through the pons and medulla. 3. Heaviest terminal labeling occurred contralaterally and in the maxillary portion of caudalis laminae III-V. Moderately dense reaction product was seen in ventral portions of all other contralateral V brain stem subnuclei, as well as in laminae I and II of caudalis. Subnucleus oralis contained the least amount of label contralateral to the injection site. Ipsilateral projections were weak and most dense in principalis. 4. Cortico-V projections were topographic between matching whisker representations. Axons most commonly had longitudinal orientations and stringy shapes. Terminal boutons occurred at the ends of short collateral branches. Many of these collaterals were derived from axons that ascended through caudal V brian stem subnuclei after crossing in the lower medulla. 5. Cortico-V labeling was heavier in septal regions between single whisker representations. This "honeycomb-like" termination pattern was most pronounced in contralateral caudalis and SpVi and ipsilateral principalis. 6. In 13 other adult rats, right SI cortex was aspirated followed by single-unit recordings in left SpVi under pentobarbital sodium anesthesia. In 9 of these, chronic effects were evaluated by recording the responses of 346 left SpVi cells 4-55 days after the lesion. In the remaining four rats, acute effects were analyzed by recording the responses of 190 SpVi cells on the day of the lesion.(ABSTRACT TRUNCATED AT 400 WORDS)

Lateral corticospinal tract

Damage to different parts of the body will cause deficits, depending on whether the damage is above (rostral) or below (caudal) the pyramidal decussation. Damage to the body above the pyramidal decussation will cause contralateral motor deficits. For example, if there is a lesion at the pre-central gyrus in the right cerebral cortex, then the left side of the body will be affected. Whereas damage below the pyramidal decussation will result in ipsilateral motor deficits. For example, spinal cord damage on the left side of the lateral corticospinal tract at the thoracic level can cause motor deficits to the left side of the body. Clinical significance

Neurology_Adams

Decorticate posturing, usually, with arm or arms in flexion and adduction and leg(s) extended, signifies lesions at a more rostral level of the nervous system—in the cerebral white matter or internal capsule and thalamus. Bilateral decorticate rigidity is essentially a bilateral spastic hemiplegia. Diagonal postures, for example, flexion of one arm and extension of the opposite arm and leg, usually indicate a supratentorial lesion. Forceful extensor postures of the arms and weak flexor responses of the legs are usually seen with lesions at about the level of the vestibular nuclei. Lesions below this level lead to flaccidity and abolition of all postures and movements. If preceded by decorticate or decerebrate postures, the coma is profound and usually progresses to brain death.

Neuroanatomy, Facial Colliculus -- Clinical Significance -- One-and-a-Half Syndrome

If a lesion in the dorsal pontine tegmentum is more extensive than the size of the CN VI nucleus and damages both the ipsilateral abducens nucleus and MLF, then the ipsilateral lateral rectus muscle and bilateral medial rectus muscles will be impaired. From the ipsilateral CN VI nucleus, CN VI fibers arise and travel to the ipsilateral lateral rectus muscle. In contrast, the interneuron fibers arising from the ipsilateral nucleus cross the midline and project through the contralateral MLF and synapse to the contralateral CN III nucleus. The ipsilateral MLF, to which the contralateral CN VI fibers project, is responsible for the synapse on the ipsilateral CN III nucleus, which innervates the ipsilateral medial rectus muscle. For example, when the lesion affects both the right CN VI nucleus and MLF fibers, the right lateral rectus and left medial rectus muscles associated with the right CN VI fibers will be impaired. The right medial rectus muscle, which is innervated by the right CN III that can no longer receive signals from the right damaged MLF, will also be impaired. As a result, when the examiner asks a patient to look to the right, the patient will seem to be looking straight ahead. When instructing a patient to look to the left, the patient’s left eye will look to the side, whereas the right eye cannot move to the left and look straight ahead.

Myelopathy

Presentation Clinical signs and symptoms depend on which spinal cord level (cervical, thoracic, or lumbar) is affected and the extent (anterior, posterior, or lateral) of the pathology, and may include: Upper motor neuron signs—weakness, spasticity, clumsiness, altered tonus, hyperreflexia and pathological reflexes, including Hoffmann's sign and inverted plantar reflex (positive Babinski sign) Lower motor neuron signs—weakness, clumsiness in the muscle group innervated at the level of spinal cord compromise, muscle atrophy, hyporeflexia, muscle hypotonicity or flaccidity, fasciculations Sensory deficits Bowel/bladder symptoms and sexual dysfunction Diagnosis


Overuse of the drugs he is taking should be suspected. Olanzapine has no antidote, so, in principle, we should antagonize the effect of benzodiazepines. If the patient continues to be drowsy and does not respond to stimuli, we should proceed to intubate to secure the airway.

A 30-year-old woman with a drug addiction PD in a current detoxification period is brought to the ED with profound somnolence, with no other symptoms. We find out that her treatment includes olanzapine and benzodiazepines. What should we do first?

ANESTHESIOLOGY, CRITICAL CARE AND EMERGENCY MEDICINE

Post-acute-withdrawal syndrome

Treatment The condition gradually improves over a period of time which can range from six months to several years in more severe cases. People with longer term and heavier substance use have caused damage to the nervous system, where, after cessation of the primary addictive substance, the opioid receptors may become favorable to any potential agonist. This places people with longer term and heavier substance use at risk of becoming addicted to any other agonist with very little use of the secondary agonist. Abstinence from all agonists, sometimes taking multiple years, is required for full recovery. Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4 to 266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

[Electrophysiologic tests and benzodiazepine hypnosis].

The effects of a pure benzodiazepine antagonist (Flumazenil) on the responses R1 and R2 of the blink reflex, psychomotor tests, and Event Related Potentials (ERP), in six healthy volunteers sedated with Midazolam have been compared. Measurements were made during each of four successive phases. Phase 0 corresponded to control recordings. Midazolam was administered rapidly during phase 1 and slowly during phase 2. Phase 3 corresponded to spontaneous waking once the administration of Midazolam had been stopped. Flumazenil was administered during phase 2. As the subjects fell asleep, R1 and R2 were the last parameters to disappear. Under the influence of Flumazenil, R1 was the first to reappear, while R2 did not recur until complete waking, and the other tests were unpracticable. During phase 3, R1 reappeared before R2 once more, the psychomotor test responses and ERP returning only later. The modifications of both R1 and R2 of the blink reflex are a good criterion of the presence of BZD in a toxic coma and a good test to indicate the depth of a coma or a sedation with BZD, whilst ERP, since they require the cooperation of the patient, are a test of vigilance and not of awakening.

[Catatonia de novo, report on a case: immediate vital prognosis and psychiatric prognosis in longer term].

We report on the case of a 20 year old woman with no previous psychiatric history, who displayed a first episode of catatonia with acute onset. Symptoms started plainly with sudden general impairment, intense asthenia, headache, abdominal pain and confusion. After 48 hours, the patient was first admitted to an emergency unit and transferred to an internal medicine ward afterwards. She kept confused. Her behaviour was bizarre with permanent swinging of pelvis, mannerism, answers off the point and increasingly poor. The general clinical examination was normal, except for the presence of a regular tachycardia (120 bpm). The paraclinical investigations also showed normal: biology, EEG, CT Scan, lumbar puncture. Confusion persisted. The patient remained stuporous, with fixed gazing and listening-like attitudes. She managed to eat and move with the help of nurses but remained bedridden. The neurological examination showed hypokinaesia, extended hypotonia, sweating, urinary incontinence, bilateral sharp reflexes with no Babinski's sign and an inexhaustible nasoorbicular reflex. The patient was mute and contrary, actively closed her eyes, but responded occasionally to simple instructions. For short moments, she suddenly engaged in inappropriate behaviors (wandering around) while connecting back to her environment answering the telephone and talking to her parents. The patient's temperature rose twice in the first days but with no specific etiology found. During the first 8 days of hospitalization, an antipsychotic treatment was administered: haloperidol 10 mg per os daily and cyamemazine 37.5 mg i.m. daily. Despite these medications, the patient worsened and was transferred to our psychiatric unit in order to manage this catatonic picture with rapid onset for which no organic etiology was found. On admission, the patient was stuporous, immobile, unresponsive to any instruction, with catalepsy, maintenance of postures, severe negativism and refusal to eat. A first treatment by benzodiazepine (clorazepate 20 mg i.v.) did not lead to any improvement. The organic investigations were completed with cerebral MRI and the ruling out of a Wilson's disease. Convulsive therapy was then decided. It proved dramatically effective from the first attempt; 4 shocks were carried out before the patient's relatives ask for her discharge from hospital. The patient revealed she had experienced low delirium during her catatonic state. The clinical picture that followed showed retardation with anxiety. She was scared with fear both for the other patients and the nursing team. She kept distant and expressed few affects. The treatment at the time of discharge was olanzapine 10 mg per os. She was discharged with a diagnosis of catatonia but with no specific psychiatric etiological diagnosis associated. She discontinued her follow-up a few weeks later. After one year, we had no information about her. Catatonia has now become rare but remains a problem for clinicians. We reviewed data concerning short term vital prognosis and psychiatric long term prognosis in catatonia. Lethal catatonia is associated with acute onset, both marked psychomotor and neurovegetative symptoms. In the light of literature, there is no proband clinical criterion during the episode that is of relevant diagnostic value to ascertain the psychiatric etiology.

Neurology_Adams

Signs of physical dependence and true addiction, although relatively rare, undoubtedly occur in chronic benzodiazepine users, even in those taking therapeutic doses. The withdrawal symptoms are much the same as those that follow the chronic use of other sedative drugs (anxiety, jitteriness, insomnia, seizures) but may not appear until the third day after the cessation of the drug and may not reach their peak of severity until the fifth day (Hollister, 1990). In chronic benzodiazepine users, the gradual tapering of dosage over a period of 1 to 2 weeks minimizes the withdrawal effects. However, we have observed numerous cases over the years in which the cessation of moderate doses of chronically used diazepines has resulted in one or more seizures. This is likely to happen when the patient is hospitalized for other reasons and the accustomed sleeping or anxiolytic medication is omitted.

Coma, Severe Hypotension, and Pinpoint Pupils After Olanzapine Intoxication in the Intensive Care Unit with Symptom Reversal After Administration of Flumazenil.

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

[Sulpiride and drug addiction].

The authors carried on their study as presented in Tunis Congress of Psychiatry and Neurology. The results of the administration of Sulpiride with drug-addicts are still difficult to evaluate, because none of the patients are hospitalized and there is no possibility to know the precise doses absorbed by the patients. An improvement is however obvious with patients who spontaneously come to ask for more. They generally present polytoxicomania and use haschisch, opium-derivatives, amphetamines and usually L.S.D. Two recent observations summarize the action of Sulpiride: 1. --A fit of acute depersonnalisation in a young lady was suppressed within eight days with the administration of 1 g p.o. of Sulpiride a day. Recovery without relapse. 2. --An old drug-addict would shoot himself i.v. with at least 1 g of Sulpiride whenever he wanted to stop his intoxication periods. He did not feel any "flash" but only could thus obtain a "soft" withdrawal without need syndrome. Neither dependence, nor serious side-effects were observed.

Coma cocktail

A coma cocktail is a combination of substances administered in an emergency to comatose individuals when the cause of the coma has not yet been determined. The intention is to work against various causes of a coma seen in an emergency setting including drug overdoses and hypoglycemia. A standard combination included dextrose (1 Amp D50W IV), flumazenil (0.2 mg IV), naloxone (2 mg IV), and thiamine (100 mg IV). It has been suggested that the use of naloxone and flumazenil be administered more selectively than glucose and thiamine. Some have proposed that the concept be abandoned completely because modern EMS providers should be able to determine the likely etiology of the change in mental status. At a minimum, the clinical presentation of the patient should rule in or out some portions of the coma cocktail. For example, with the advent and widespread implementation of glucometers, the indications for administering glucose can be more narrowly defined and its use more regimented.

Schneiderian first-rank symptoms caused by benzodiazepine withdrawal.

Benzodiazepine withdrawal has been found to give rise to numerous physical and psychological symptoms. This paper describes, for the first time, Schneiderian first-rank symptoms of schizophrenia caused by such withdrawal.

Central nervous system depression

There are two antidotes that are frequently used in the hospital setting and these are naloxone and flumazenil. Naloxone is an opioid antagonist and reverses the central nervous depressive effects seen in opioid overdose. In the setting of a colonoscopy, naloxone is rarely administered but when it is administered, its half-life is shorter than some common opioid agonists. Therefore, the patient may still exhibit central nervous system depression after the naloxone has been cleared. Naloxone is typically administered in short intervals with relatively small doses in order to prevent the occurrence of withdrawal, pain, and sympathetic nervous system activation. Flumazenil is a benzodiazepine antagonist and blocks the binding of benzodiazepines to gamma-aminobutyric acid receptors. Similarly to naloxone, flumazenil has a short half-life, and this needs to be taken into account because the patient may exhibit central nervous depression after the antidote has been cleared. Benzodiazepines

[The use of olanzapine in sleep disorders. An open trial with nine patients].

The impossibility of treating patients with sleep disorders adequately means that, as specialists, we have to look for new pharmacological treatments and for this reason we examined the information in the paper by Salin Pascual (1999) about the increase in deep sleep when olanzapine is used as an antipsychotic drug. We decided to use this medication in six females and three males who were suffering from different sleep disorders that conditioned their chronic insomnia. The dosages of olanzapine used ranged from 2.5 and 10 mg in a single dose. The clinical history and progress were used to elaborate the results and conclusions. The result was positive in eight of the nine patients, five who were administered the medication as monotherapy and three as polytherapy. The population studied is insufficient to prove the effectiveness of the drug, but the fact that in eight of our patients the treatment clearly improved their symptoms leads us to think that this line of research must be continued.

Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification.

Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.

[Flumazenil, a benzodiazepine antagonist, in endoscopic premedication].

Midazolam is the benzodiazepine recommended for anaesthesia induction when an early recovering is desirable. Flumazenil, which is also a hydrosoluble imidazobenzodiazepine, improves the safety of the forhere one because it immediately reduces the degree of sedation. With this purpose, this last drug has been studied in 25 patients who had been previously treated with Midazolam in order to carry out different endoscopic studies. The Flumazenil average dose used was 0.276 mg and the conscience recovering after its intravenous injection, evaluated by a simple oral numeric regression test, oscillated between 60 and 300 seconds with an X of 96 seconds. Once the study was finished, all patients were discharged from hospital after two-hour observation, except for one patient (4%) who suffered a complication and so was discharged after a twenty-four-hour control. No doubt the advent of a drug opposed to benzodiazepine receptors used in anaesthetic induction shows the possibility of a quick recovering and moreover. Quicker discharge from hospital.

Nonbenzodiazepine

The Z-drug zaleplon may have fewer side effects compared to benzodiazepines. Dependence and withdrawal management Nonbenzodiazepines should not be discontinued abruptly if taken for more than a few weeks due to the risk of rebound withdrawal effects and acute withdrawal reactions, which may resemble those seen during benzodiazepine withdrawal. Treatment usually entails gradually reducing the dosage over a period of weeks or several months depending on the individual, dosage, and length of time the drug has been taken. If this approach fails, a crossover to a benzodiazepine equivalent dose of a long-acting benzodiazepine (such as chlordiazepoxide or more preferably diazepam) can be tried followed by a gradual reduction in dosage. In extreme cases and, in particular, where severe addiction and/or abuse is manifested, an inpatient detoxification may be required, with flumazenil as a possible detoxification tool.

"First Things First": What is the First Thing?

This op-ed piece comments on the down-side of an otherwise useful 12-step slogan, "First Things First," which generally refers to staying sober (not drinking or using no matter what). While important, there are environmental, microsocial, psychiatric, and neurobiological considerations that may place other needs at an equal or higher priority than sobriety per se. That is, other changes may be needed to set the stage for, or enhance efforts at sobriety, prior to or concurrent with attempting to quit one's drug of choice. Perhaps slogans should be considered in a broader context and not be taken too literally.

Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management.

The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected ingestion of dextromethorphan by 1) describing the process by which an ingestion of dextromethorphan might be managed, 2) identifying the key decision elements in managing cases of dextromethorphan ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to the ingestion of dextromethorphan alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) Patients who exhibit more than mild effects (e.g., infrequent vomiting or somnolence [lightly sedated and arousable with speaking voice or light touch]) after an acute dextromethorphan ingestion should be referred to an emergency department (Grade C). 3) Patients who have ingested 5-7.5 mg/kg should receive poison center-initiated follow-up approximately every 2 hours for up to 4 hours after ingestion. Refer to an emergency department if more than mild symptoms develop (Grade D). 4) Patients who have ingested more than 7.5 mg/kg should be referred to an emergency department for evaluation (Grade C). 5) If the patient is taking other medications likely to interact with dextromethorphan and cause serotonin syndrome, such as monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, poison center-initiated follow-up every 2 hours for 8 hours is recommended (Grade D). 6) Patients who are asymptomatic and more than 4 hours have elapsed since the time of ingestion can be observed at home (Grade C). 7) Do not induce emesis (Grade D). 8) Do not use activated charcoal at home. Activated charcoal can be administered to asymptomatic patients who have ingested overdoses of dextromethorphan within the preceding hour. Its administration, if available, should only be carried out by health professionals and only if no contraindications are present. Do not delay transportation in order to administer activated charcoal (Grade D). 9) For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered for prehospital administration, particularly if the patient has respiratory depression (Grade C). 10) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104 degrees F, >40 degrees C) for serotonin syndrome. This should be done in consultation with and authorized by EMS medical direction, by a written treatment protocol or policy, or with direct medical oversight (Grade C). 11) Carefully ascertain by history whether other drugs, such as acetaminophen, were involved in the incident and assess the risk for toxicity or for a drug interaction.

Orbital (band)

In late 1992, the Radiccio EP barely reached the UK top 40, although it included one of their most popular songs, "Halcyon". The track featured a sample of Kirsty Hawkshaw from "It's a Fine Day" (a chart hit for Opus III earlier that year). The B-side "The Naked and the Dead" was similarly based on a line from Scott Walker's rendition of Jacques Brel's song "Next". "Halcyon" was dedicated to the Hartnolls' mother, who was addicted to the tranquiliser Halcion (Triazolam) for many years.

Flumazenil -- Administration -- Dosing: Adult

FDA Dosage for management of benzodiazepine overdose The clinician should give the initial dosage of 0.2 mg IV for 30 seconds If the desired level of consciousness is not obtained after 30 seconds, the clinician can give an additional dose of 0.3 mg IV over 30 seconds May repeat doses of 0.5 mg IV over 30 seconds at 1-minute intervals to a maximum total cumulative dose of 3 mg Patients with partial response to 3 mg may require additional slow titration up to a total dose of 5 mg. If there is no response after administration of 5 mg, the primary cause of sedation is not benzodiazepine-related, and further treatment with Flumazenil will be ineffective. In reoccurrence, sedations repeat doses may be given at 20-minute intervals, not to exceed 1 mg (0.5 mg/minute) per dose or 3 mg/hour. FDA dosage for benzodiazepine reversal when used in conscious sedation or general anesthesia

Chlordiazepoxide

Chlordiazepoxide taken during pregnancy can cause a postnatal benzodiazepine withdrawal syndrome. Overdose An individual who has consumed excess chlordiazepoxide may display some of the following symptoms: Somnolence (difficulty staying awake) Mental confusion Hypotension Hypoventilation Impaired motor functions Impaired reflexes Impaired coordination Impaired balance Dizziness Muscle weakness Coma Chlordiazepoxide is a drug that is very frequently involved in drug intoxication, including overdose. Chlordiazepoxide overdose is considered a medical emergency and, in general, requires the immediate attention of medical personnel. The antidote for an overdose of chlordiazepoxide (or any other benzodiazepine) is flumazenil. Flumazenil should be given with caution as it may precipitate severe withdrawal symptoms in benzodiazepine-dependent individuals.

Neurology_Adams

Most patients during withdrawal do not require antiepileptic drugs, as the entire episode of seizure activity—whether a single seizure or a brief flurry of seizures—may have terminated before the patient is brought to medical attention. The parenteral administration of diazepam or sodium phenobarbital early in the withdrawal period does, however, prevent withdrawal fits in patients with a previous history of this disorder, as well as in those who might be expected to develop seizures on withdrawal of alcohol. This approach has been supported by the observations of D’Onofrio and colleagues that intravenous lorazepam (2 mg in 2 mL of normal saline) was highly effective in preventing recurrent seizures after a first seizure in the same withdrawal period. Only 3 of 100 patients so treated had a second seizure within 48 h, compared to 21 of 86 untreated patients. The long-term administration of anticonvulsants is neither necessary nor practical: if such patients remain abstinent, they will

Buprenorphine

In the years before buprenorphine/naloxone was approved, Reckitt Benckiser had lobbied Congress to help craft the Drug Addiction Treatment Act of 2000, which gave authority to the Secretary of Health and Human Services to grant a waiver to physicians with certain training to prescribe and administer schedule III, IV, or V narcotic drugs for the treatment of addiction or detoxification. Before this law was passed, such treatment was permitted only in clinics designed specifically for drug addiction.

Dose Calculation Desired Over Have Formula Method -- Technique or Treatment -- Dimensional Analysis Method

An order placed by a provider for lorazepam 4 mg IV PUSH for CIWA score of 25 or higher, follow CAGE Protocol for subsequent dosages based on CIWA scoring. The clinician has 2 mg/mL vials in the automated dispensing unit. How many milliliters are needed to arrive at an ordered dose? The desired dose os placed over 1 remember, (x mL) = 4 mg/1 x 1 mL/2 mg x (4)(1)/2 x 4/2 x 2/1 = 2 mL, keep multiplying/dividing until the desired amount is reached, 2 mL in this example. Notice, the fraction was set up with milligrams and milligrams strategically placed, so units could cancel each other out, making the equation easier to solve for the unit desired or milliliters. The answer makes sense, so work is done. Zeros can be canceled out in the same way as like units. For example: 1000/500 x 10/5 = 2, the 2 zeros in 1000 and 2 zeros in 500 can be crossed out since like units in numerator and denominator, leaving 10/5, a much easier fraction to solve, and the answer makes sense.

Addiction of High Dose of Benzodiazepine: Verona Detox Approach With Flumazenil.

Since the 1990s there has been evidence of the significant role Flumazenil (FLU) has in benzodiazepines (BZD) detoxes. The Verona Detox approach has been developed for high dose BZD and Z-drug detoxification via continuous subcutaneous infusion of FLU, a selective BZD receptor antagonist acting on the BZD subunit of the GABA-A receptor. Flumazenil is licensed in the United Kingdom and other countries to treat only BZD overdose although numerous studies have demonstrated its effectiveness in rapidly resetting GABA-A receptors, quickly reducing tolerance and dependence from BZD, and providing a safe and rapid detox from benzodiazepines. The aim of this article is to provide all healthcare professional who are interested in BZD detoxification with an approach and clear practical information on how to administer FLU. In this article we outline the approach in detail, describing all medical and nursing procedures day by day. This detox treatment is indicated for patients abusing from at least 5 Defined Daily Dose (DDD) of BZDs or Z-drugs. The process lasts 7 days, and is conducted under medical supervision (daily reviews) and continuous nursing (24/7). During this period, 7mg of FLU is administered (1 mg/24) through an elastomeric pump, via continuous subcutaneous infusion. To this day, the largest database of FLU detoxification was published by our group, showing how this treatment is safe, with very little side effects even in patients with significant medical comorbidities.

Four Good Days

antagonist in order to help her on the road to sobriety. However, she must stay off any drugs for an additional four days before it is safe for her to receive the first shot, and then expect an additional shot each month.

[Prescription of olanzapine in children and adolescent psychiatric patients].

A review of the literature from 1996-2004 on the indications and adverse reactions concerning the use of olanzapine, a second generation antipsychotic agent, in children and adolescents with psychiatric illness is made in this article. Studies lasted for 2 to 3 months and a few had a follow up period up to a year. Olanzapine, dosed from 2.5 to 20 mg/day, is shown to be a useful drug in the treatment of child and adolescent onset schizophrenia, bipolar disorder, anorexia nervosa with delusions, pervasive developmental disorder, tic disorders, and aggression. OPEN AND DOUBLE-BLIND STUDIES: In 4 open labeled studies (26, 34, 39, 43) and 2 case reports (25), 53 patients, aged from 6-18 years old, afflicted by child onset schizophrenia, were treated with olanzapine for 1 1/2 weeks to one year; 19 had treatment resistant childhood schizophrenia and 34 a first episode. In the first group 13/19 showed improvement whereas, in the second group 27/34 were considered responders. Four patients in the first group who had responded to clozapine (stopped because of adverse events) did less well on olanzapine. In 5 studies, 4 open labeled (15, 20, 44) and 1 double blind (27), 59 adolescent onset schizophrenic patients were treated by olanzapine from 8 to 26 weeks; 50/59 patients were considered responders. In the open label study (20) comparing 43 adolescents treated by olanzapine (19 patients), risperidone (17 patients), or haloperidol (7 patients), improvement was significant in the three groups after 4 weeks of treatment and continued after 8 weeks. It is most interesting to mention that 2 months after the end of the study 71% (12/17) of the olanzapine group that had completed the study, 10/15 (67%) of the risperidone group, and 43% (3/7) of the haloperidol group had continued their treatment. Dropouts were for inefficacy and non-compliance in the olanzapine and risperidone groups whereas they were also for adverse events in the haloperidol group (2/4). A final double blind study of 263 adult and adolescent schizophrenic patients (latter are not separated from the former) confirmed the superiority of olanzapine compared to haloperidol and its use for a long period: 67% of the olanzapine and 54% of the haloperidol patients completed the 12-week study. 12 case reports of children and adolescents diagnosed with acute mania (8, 25, 46, 47) and 23 in an open labeled study (16) were treated by olanzapine; 26/35 were considered to respond well. Some of the patients were on mood stabilizers before adjunction of olanzapine, others on olanzapine monotherapy; 10 case reports of patients with anorexia nervosa associated with psychotic symptomatology, aged from 10-17 years old, relate the use of olanzapine as adjuvant treatment. Improvement was spectacular in these patients who not only gained considerable weight, but were also more compliant to the therapeutic program and their obsessions, delusions, agitation and anxiety became less intense. In this form of anorexia nervosa, olanzapine appears to have an interesting therapeutic role and, in particular, its most important adverse effect, weight gain, became a therapeutic goal. In 2 preliminary studies (24, 30) 31 children and adolescents diagnosed with pervasive developmental disorder were treated by olanzapine from 6 to 13 weeks; 18/25 had good or moderate symptomatic improvement: they were less irritable and hyperactive, and their speech less excessive. In 17 case reports of children and adolescents with aggression (42, 45), associated with tics in 10 patients (49), treatment with olanzapine from 2 weeks to 10 months lowered the presenting symptoms, enhanced the cooperation, and improved the mood of the patients. Only one patient's treatment was changed for inefficacy. No matter what the disorder treated, when olanzapine was compared to haloperidol and risperidone, it proved to be as effective as risperidone, and as or more effective than haloperidol; but when compared to clozapine, it was less effective. The most prominent adverse reaction was excessive weight gain, even more so than in adult patients treated with olanzapine. Also weight gain was greater in children and adolescents treated by olanzapine than those treated by risperidone or haloperidol. Though few treatments had to be interrupted because of this side effect, child and adolescent psychiatrists are wary of the long-term disease related to obesity and glucose dysregulation. All should be done to under-stand the process of weight gain better and to prevent or stall excessive caloric intake, encourage activity, and eventually treat by corrector drugs. Secondly, sedation may bother up to 50% of patients even at the end of the study periods, as many as those treated by haloperidol and more than those treated by risperidone. Extrapyramidal symptoms were mild or moderate compared to those that appear with haloperidol, but may be more frequent than in adult patients. Liver enzymes and blood sugar may be slightly elevated. Prolactemia may be elevated but less so with risperidone and haloperidol. All the authors emphasized the unfortunate lack of randomized double blind studies for the use of olanzapine in this age group.

A Case of Phenibut Directed Detoxification Leading to Toxicity During the COVID-19 Pandemic.

Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman's self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic. A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. She chose self-directed detoxification as she feared COVID-19 exposure in detoxification facilities. Her altered mental status drove her to jump out a third-story window causing multiple spinal fractures. After a long hospitalization, she self-directed her discharge home due to concerns about COVID-19. Her premature discharge disrupted opioid and benzodiazepine use disorder treatment plans. This case highlights the risks of phenibut use for selfdirected detoxification. With COVID-19 related changes in the drug supply, people may be more likely to use online pharmaceuticals, therefore, substance use assessments should inquire about the online acquisition of new psychoactive drugs. Public health messaging regarding the risks of infectious disease transmission in addiction care settings is needed to guide addiction treatment choices among people who use substances.

The Mystery of Edwin Drood

Princess Puffer tries to follow Jasper, she suspects him of something because of what he said during his opium intoxication. Jasper says to Puffer at the end of what exists of the book: "Suppose you had something in your mind; something you were going to do... Should you do it in your fancy, when you were lying here doing this?... I did it over and over again. I have done it hundreds of thousands of times in this room." The very first hint (Mr. Jasper being concerned about what he may say while in an opium stupor) occurs in the first pages when Mr. Jasper listens to other opium users and says "unintelligible!". On his last opium trip, Puffer says to him, while he sleeps: "'Unintelligible' I heard you say, of two more than me. But don't ye be too sure always; don't ye be too sure, beauty!" Lastly, on the day of Edwin's disappearance, Jasper was in an ebullient state of mind all day, performing in the choir with great self-command.

Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial.

To assess the efficacy of ivermectin in addition to standard treatment compared to standard treatment alone in reducing hospitalizations in the COVID-19 patient population. IVERCOR-COVID19 will be a single-center, prospective, randomized, double-blind, parallel group (1:1 ratio), placebo-controlled study. Patients who meet the following criteria will be invited to participate: Inclusion criteria: (1) Over 18 years of age who reside in the province of Corrientes at the time of diagnosis. (2) Confirmed diagnosis of COVID-19 by polymerase chain reaction (PCR) test for detection of SARS-CoV2 in the last 48 h. (3) In the case of women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study and for the entire period of time for the duration of the study and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study). (4) Weight at the time of inclusion greater than 48 kg. (5) That they sign the informed consent for participation in the study. (1) pregnant or breastfeeding women; (2) known allergy to ivermectin or some of the components of ivermectin tablets or placebo; (3) current use of home oxygen; (4) require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19; (5) presence of mal-absorptive syndrome; (6) presence of any other concomitant acute infectious disease; (7) known history of severe liver disease, for example liver cirrhosis; (8) need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19; (9) need or use of hydroxychloroquine or chloroquine; (10) use of ivermectin up to 7 days prior to randomization; (11) patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months; and (12) current participation or in the last 30 days in a research study that has included the administration of a drug (Table 1). Table 1 Ivermectin/placebo dose according to patient weight Patient weight Ivermectin/placebo dose Total dose (mg) Equal to or greater than 48 kg and less than 80 kg 2 tablets of 6 mg each at the time of inclusion and 2 tablets 24 h after the first intake 24 Equal or greater than 80 kg and less than 110 kg 3 tablets of 6 mg each at the time of inclusion and 3 tablets 24 h after the first intake 36 Equal or greater than 110 kg 4 tablets of 6 mg each at the time of inclusion and 4 tablets 24 h after the first intake 48 The study will be carried out by the Ministry of Public Health of the Province of Corrientes (Argentina) in coordination with the Institute of Cardiology of Corrientes in the Province of Corrientes, Argentina. Intervention group: patients who are randomized to ivermectin will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg ivermectin; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of ivermectin; patients weighing more than 110 kg will receive 4 tablets of 6 mg ivermectin) the day they enter the study and the same dose 24 h after the first dose. patients who are randomized to placebo will receive the dose according to their weight (patients up to 80 kg will receive 2 tablets of 6 mg placebo; patients with more than 80 kg and up to 110 kg will receive 3 tablets of 6 mg of placebo; patients weighing more than 110 kg will receive 4 tablets of 6 mg placebo) on the day they enter the study and the same dose 24 h after the first dose (Table 2). Table 2 Inclusion and exclusion criteria Inclusion criteria Exclusion criteria 1. Over 18 years of age who reside in the province of Corrientes at the time of diagnosis 1. Pregnant or breastfeeding women 2.Confirmed diagnosis of COVID-19 by polymerase chain reaction test for detection of SARS-CoV2 in the last 48 h 2. Known allergy to ivermectin or some of the components of ivermectin tablets or placebo 3. In case of being women of childbearing age, they must be using a contraceptive method of proven efficacy and safety (barrier, hormonal, or permanent contraceptives) for at least 3 months prior to inclusion in the present study, during the entire period of time for the duration of the study, and until at least 30 days after the end of this study. A woman will be considered to have no reproductive capacity if she is postmenopausal (at least 2 years without her menstrual cycles) or if she has undergone surgical sterilization (at least 1 month before the time of inviting her to participate in this study) 3. Current use of home oxygen 4. Weight at the time of inclusion equal to or greater than 48 kg 4. That require hospitalization due to COVID-19 at the time of diagnosis or history of hospitalization for COVID-19 5. That they sign the informed consent for participation in the study 5. Presence of mal-absorptive syndrome 6. Presence of any other concomitant acute infectious disease 7. Known history of severe liver disease, for example liver cirrhosis 8. Need or use of antiviral drugs at the time of admission for another viral pathology other than COVID-19 9. Need or use of hydroxychloroquine or chloroquine 10. Use of ivermectin up to 7 days prior to randomization 11. Patients on dialysis or who have required it in the last 2 months or who plan to do it in the next 2 months 12. Current participation or in the last 30 days in a research study that has included the administration of a drug MAIN OUTCOMES: Primary outcome will be the percentage of hospitalizations in patients with COVID-19 in the intervention and control groups. time to hospitalization in each of the arms of the study: number of days elapsed from the inclusion in the study until the hospitalization of the patient; percentage of use of invasive mechanical ventilation in each of the study arms: every patient who is connected to invasive mechanical ventilation after signing the informed consent and before the final study visit; time to invasive mechanical ventilation in each of the arms of the study: number of days elapsed from inclusion in the study to connection to invasive mechanical ventilation of the patient; percentage of patients requiring dialysis in each of the study arms: all patients who require renal replacement therapy of any kind, temporary or permanent, and which begins after signing the informed consent and before the final visit; mortality from all causes in each of the two trial groups: death of the patient, from any cause. Negative PCR swab at 3 ± 1 and 12 ± 2 days after entering the study. Ivermectin safety: it will be analyzed according to the incidence of adverse events that patients present in the intervention and control groups. The end of study (EOS) is recorded as the day the patient is discharged or death. Discharge will be granted according to the current recommendations of the Ministry of Public Health of the Province of Corrientes. A follow-up visit (EOF) will be made by phone 30 days after the EOS when vital status will be verified. Randomization will be done through a web system with randomly permuted blocks. Randomization will be carried out by one of the investigators who will not participate in the inclusion of patients or in the delivery of medication (Table 3). Table 3 EOS end of study, EOF end of follow-up Visit Basal and randomization, day 0 Day 3 ± 1 Day 12 ± 2 V#1 V#2 V#3 EOS EOF Informed consent X - - - - Inclusion/exclusion criteria X - - - - Demographic data and medical history X - - - - Concomitant medication X - - - - Vital signs* X X - - - Anthropometric data<sup^</sup X - - - - Basal laboratory X - - - - PCR swab - X X - - Assessment of adverse events - X X X - Final objective evaluation - X X X X Randomization X - - - - Adherence to treatment X X - - - *Includes heart rate, temperature, and oxygen saturation by a digital saturometer ^Includes weight and height BLINDING (MASKING): The participants, investigators, care providers, and outcome assessors will be blinded. We will include a total of 500 patients (250 patients in each group). This is version 1.0, 17 August 2020. The recruitment started on 19 August 2020, and we anticipate the trial will finish recruitment on 31 December 2020. ClinicalTrials.gov NCT04529525 . Registered on 26 August 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

David J. Impastato

Zigmond Lebensohn, MD, provides specifics in his account of the event in Comprehensive Psychiatry: "Dr Impastato's records reveal the following handwritten entry for January 7, 1940: 'Volts 70, T-.1 sec MA 400. Had delayed (15sec?) reaction during apnea, face flushed, eyes opened, normal expression–looking forward, no breathing.' This treatment was administered by Dr. Impastato on a Sunday morning in his office."

Effect of flumazenil on basal and naloxone-stimulated ACTH and cortisol release in humans.

1. Endogenous benzodiazepine receptor ligands are thought to influence the human hypothalamic-pituitary-adrenal (HPA) axis and naloxone, a known stimulator of adrenocorticotropic hormone (ACTH) release, is thought to act via release of hypothalamic corticotropin-releasing hormone. 2. The aim of the present study was to assess the influence of endogenous benzodiazepine-receptor ligands by administering flumazenil (Ro15-1788), a benzodiazepine antagonist, and measuring ACTH and cortisol release, both basal and during naloxone-stimulation. 3. Nine normal volunteers in a placebo-controlled double-blind design were studied. Flumazenil (0.5 mg, i.v. bolus) was given 2 min before naloxone (125 micrograms/kg bodyweight, i.v. bolus) immunoreactive-adrenocorticotropic hormone (IR-ACTH) and cortisol levels were measured at frequent intervals from 60 min before to 120 min after naloxone injection. 4. Flumazenil had no effect on ACTH and cortisol release when given alone; flumazenil area under the ACTH/time curve (pmol/L.min) = -36.5 +/- 63.5 compared with placebo = -53.5 +/- 31.8, flumazenil area under the cortisol/time curve (nmol/L.min x 10(-3)) = - 2.4 +/- 2.4 compared with placebo -0.56 +/- 1.4. Flumazenil did not change the ACTH and cortisol release achieved with naloxone; naloxone area under the ACTH/time curve (pmol/L.min) = 327.8 +/- 61.7 compared with flumazenil/naloxone = 366.3 +/- 88.1, naloxone area under the cortisol/time curve (nmol/L. min x 10(-3) = 12.2 +/- 3.4 compared with naloxone/flumazenil = 10.5 +/- 2.1. 5. The authors conclude that flumazenil dose not modify basal or stimulated ACTH and cortisol release in healthy humans. This would suggest that endogenous benzodiazepine-like ligands and the benzodiazepine/gamma-aminobutyric acid receptor complex do not tonically influence the hypothalamic-pituitary-adrenal axis.

[Sedation in endoscopic diagnosis: rationale of the use of specific benzodiazepine antagonists].

The aim of this study was to evaluate the best clinical use of Flumazenil, a specific antagonist of benzodiazepines, during endoscopic exams. Two-hundred patients were studied: 120 were treated with Flumazenil and 80 with placebo. The patients were prepared for the endoscopic exam with local anaesthesia and i.v. Diazepam administration. Controls performed at the end of the exam and at 5, 30, 120 e 240 minutes from the administration of Flumazenil and placebo, allowed to evaluate the state of awakeness, the level of conscience and the capacity of time-space orientation. Significantly statistical differences between the two groups were obtained at 5, 30 and 120 minutes after Flumazenil administration, while both groups had retrograde amnesia. The drug was well tolerated and there were no undesiderable side effects or reactions. The Authors therefore affirm that Flumazenil, in virtue of its competitive action toward benzodiazepine receptors, interrupts sedation with immediate awakening and improvement of the state of consciousness. Such drug, thus, permits the Day Hospital performance of endoscopic procedures which otherwise would require hospitalization, at the same time allowing the surgeon to use benzodiazepines at doses more adequate for surgical necessities.

Prompt improvement of difficulty with sleep initiation and waking up in the morning and daytime somnolence by combination therapy of suvorexant and ramelteon in delayed sleep-wake phase disorder: a case series of three patients.

Patients with delayed sleep-wake phase disorder (DSWPD) suffer from difficulties in sleep initiation at night, difficulties in waking up at the socially required time, and daytime somnolence. About half of the patients resist conventional light therapy and melatonin therapy. Therapy using hypnotics is not recommended due to its adverse effects. Recently, suvorexant, an orexin receptor antagonist, has become available for clinical use. The drug is relatively safer than traditional hypnotics such as benzodiazepines. We report three DSWPD patients who were successfully treated by the combination therapy of suvorexant and ramelteon. The first case was a 19-year-old woman who was experiencing difficulties in sleep initiation, difficulty in waking up in the morning, and daytime somnolence. She showed a prompt response to the combination therapy of suvorexant and ramelteon. Her sleep phase advanced, and her daytime somnolence reduced. The second and third cases were 21-year-old and 17-year-old men, respectively, who also showed significant sleep phase advances. Although case 2 was resistant to ramelteon treatment, his sleep phase advanced after suvorexant started. His difficulty in falling asleep and his habit of daytime napping disappeared after the combination therapy of suvorexant and ramelteon was started. Case 3 also showed a prompt response. His difficulties in falling asleep and waking up in the morning were ameliorated immediately after suvorexant with ramelteon was started. No obvious side effects were observed. Therapy using the combination therapy of suvorexant and ramelteon might be a reasonable option for DSWPD patients.

First_Aid_Step2

A schizophrenic patient takes haloperidol for one year and develops uncontrollable tongue movements. Diagnosis? Treatment? A man unexpectedly ﬂies across the country, takes a new name, and has no memory of his prior life. Panic disorder. Agranulocytosis. Schizophreniform disorder (diagnosis of schizophrenia requires ≥ 6 months of symptoms). Weight gain, type 2 DM, QT prolongation. Acute dystonia (oculogyric crisis). Treat with benztropine or diphenhydramine. Neuroleptics. Conduct disorder. Rett’s disorder. Acute mania. Start a mood stabilizer (e.g., lithium). Malingering. Factitious disorder (Munchausen syndrome). Substance abuse. Phencyclidine hydrochloride (PCP) intoxication. Depersonalization disorder. Frotteurism (a paraphilia). Tardive dyskinesia. ↓ or discontinue haloperidol and consider another antipsychotic (e.g., risperidone, clozapine). Dissociative fugue. Risk factors for DVT. Criteria for exudative effusion. Causes of exudative effusion.