Secondary hypersomnia as an initial manifestation of neuromyelitis optica spectrum disorders.

The identification of AQP4-IgG, a specific and pathogenic antibody of NMO/SD has led to a broadening of the clinical spectrum of manifestations of NMO/SD including the presence of encephalic symptoms. Lesions are often distributed on peri­ependymal area and sometimes affected the diencephalon leading to sleep disorders. We report a case of hypersomnia with polysomnographic documentation during the first attack of NMO/SD. Brain MRI revealed bilateral hypothalamic lesions around the third ventricle, whereas optic nerves and spinal cord were intact. The record of the nocturnal video-polysomnography followed by multiple sleep latency tests (MSLT) revealed an abnormal shortened sleep period with a single sleep onset in REM allowing secondary central hypersomnia diagnosis. The recovery of hypersomnia was complete within few months without psychostimulant treatment and the diencephalic lesion disappeared. Thus, diencephalic form of NMO/SD seems to cause narcolepsy or non-narcoleptic central hypersomnia and have a good recovery.

Cognitive decline and hypersomnolence: thalamic manifestations of a tentorial dural arteriovenous fistula (dAVF).

BACKGROUND: Intracranial dural arteriovenous fistulas (dAVFs) often present with pulsatile tinnitus, orbital congestion, and headache. Occasionally, they present with focal neurologic deficits, a dementia-like syndrome, hemorrhage, or ischemic infarction. METHODS: This study is based on the case of a 71-year-old gentleman who presented with 6 months of progressive forgetfulness, inattention, and hypersomnolence. Four weeks prior to presentation, he developed symptoms of left-sided pain, numbness, and worsening weakness. Neurologic examination demonstrated hypersomnolence, a score of 30/38 on the Kokmen Short Test of Mental Status, and left hemiparesis. MRI brain revealed bilateral thalamic T2 hyperintensities with associated enhancement. MR venogram (MRV) showed a vascular malformation in the posterior fossa and occlusion of the straight sinus. Conventional cerebral angiogram confirmed a tentorial dAVF. The dAVF was definitively treated with transarterial embolization, followed by clip ligation of the arterialized draining vein. Twelve weeks later, there was clinical resolution of left hemiparesis and improvement in cognitive status. MRI revealed complete resolution of the thalamic hyperintensities. MRV demonstrated recanalization of the straight sinus. RESULTS: Intracranial dAVFs are uncommon but potentially life-threatening acquired vascular malformations. The initiating factor is venous hypertension, causing retrograde flow, venous congestion, ischemia, and sometimes infarction. The spectrum of clinical manifestations in dAVFs reflects the degree of venous congestion present. If retrograde venous flow is surgically obliterated, then venous hypertension may be reversible. Bilateral thalamic venous congestion can present as a thalamic dementia. CONCLUSION: We conclude that intracranial dAVFs with thalamic venous congestion should be considered in the diagnostic differential for patients who present with subacute cognitive decline and T2 hyperintense thalamic signal change.

Hypothermia, hypotension, hypersomnia, and obesity associated with hypothalamic lesions in a patient positive for the anti-aquaporin 4 antibody: a case report and literature review.

OBJECTIVE: To describe a patient positive for the anti-aquaporin 4 antibody with hypothalamic lesions showing hypothermia, hypotension, hypersomnia, and obesity. DESIGN: Case report. SETTING: University hospital. PATIENT: We describe a 21-year-old woman who was positive for anti-aquaporin 4 antibody and presented with hypothermia, hypotension, and hypersomnia owing to bilateral hypothalamic lesions as the only abnormal clinical finding. RESULTS: Immediate steroid administration resulted in significant improvement of the patient's vital signs and imaging findings; however, her cognitive impairment and sleepiness persisted, and she subsequently developed obesity. Decreased cerebrospinal fluid orexin levels and sleep studies confirmed the diagnosis of narcolepsy due to medical condition. Physicians should be aware that neuromyelitis optica spectrum disorders can initially involve the hypothalamus. CONCLUSIONS: We emphasize that measurement of anti-aquaporin 4 antibody is of clinical importance in the differential diagnosis of hypothalamic lesions.

A patient with anti-aquaporin 4 antibody presenting hypersomnolence as the initial symptom and symmetrical hypothalamic lesions.

Here we report a case with positive serum anti-aquaporin 4 (AQP4) antibody who presented with hypersomnolence, symmetrical hypothalamic lesions and a reduced CSF orexin (hypocretin) level without optic nerve and spinal cord lesions on MRI. All of the symptoms, MRI finding and CSF orexin level improved simultaneously after steroid therapy. AQP4 is a member of the AQP superfamily which is strongly expressed in the hypothalamus where orexin (hypocretin)-containing neurons are primarily concentrated. Although there have been only a few reports similar to our case, the present case suggests a close relationship between the positive serum anti-AQP4 antibody and symmetrical hypothalamic lesions with hypersomnolence and without optic /spinal lesion, which is improved by steroid treatment.

The pathophysiologic basis of secondary narcolepsy and hypersomnia.

The symptoms of narcolepsy can occur during the course of other neurologic conditions (ie, symptomatic narcolepsy). Inherited disorders, tumors, and head trauma were the three most frequent causes for symptomatic narcolepsy. Other causes include multiple sclerosis (MS), vascular disorders, and encephalitis. Cerebrospinal fluid hypocretin-1 measures were carried out in some recent cases with symptomatic narcolepsy, and moderate decreases in hypocretin levels were seen in a large majority of these cases. Excessive daytime sleepiness (EDS) in these symptomatic cases was sometimes reversible with an improvement of the causative neurologic disorder and with an improvement of the hypocretin (orexin) status. Recently, we found that several symptomatic narcoleptic cases with MS show unique bilateral symmetric hypothalamic lesions associated with significant hypocretin ligand deficiency. In addition, these patients often share the clinical characteristics of neuromyelitis optica (NMO) and the detection of NMO-IgG (or anti-aquaporin-4 [AQP4] antibodies), suggesting a new clinical entity. Further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiologic mechanisms for occurrence of EDS and cataplexy.

A patient with anti-aquaporin 4 antibody who presented with recurrent hypersomnia, reduced orexin (hypocretin) level, and symmetrical hypothalamic lesions.

Recent studies have demonstrated that hypothalamic lesions associated with brain tumor, head trauma, and encephalopathy can cause symptomatic hypersomnia with a reduced orexin (hypocretin) level in the cerebrospinal fluid (CSF). Aquaporin 4 (AQP4), a member of the AQP superfamily, is strongly expressed in the hypothalamus in which orexin (hypocretin)-containing neurons are primarily concentrated. We report the case of a patient with a serum anti-AQP4 antibody who presented with recurrent hypersomnia, symmetrical hypothalamic lesions with long spinal cord lesions on MRI, and a reduced CSF orexin (hypocretin) level, all of which were improved simultaneously by steroid therapy. Further studies should be performed to determine the roles of anti-AQP4 antibody positivity in patients with hypersomnia associated with orexin (hypocretin) deficiency and hypothalamic lesions.

Characterization of the melanin-concentrating hormone neurons activated during paradoxical sleep hypersomnia in rats.

Although the main nodes of the neuronal network that regulate paradoxical sleep (PS), also called rapid eye movement sleep, have been identified in rodents, it still needs to be more thoroughly described. We have recently shown that 58% of a hypothalamic neuronal population, the melanin-concentrating hormone (MCH) neurons, are activated after a PS hypersomnia and that MCH, when injected intracerebroventricularly, induces a dose-dependent increase in PS. This suggests that MCH plays a role in PS regulation. Two subpopulations of MCH neurons have been distinguished neurochemically, one that coexpresses cocaine and amphetamine-regulated transcript (CART) and sends ascending projections to the septum and the hippocampus, the other, the non-CART MCH neurons, send descending projections to the lower brainstem and the spinal cord. In order to better characterize the PS-activated MCH neurons it is interesting to determine whether they belong to the first, the second, or both subgroups. We therefore undertook an MCH, CART, and Fos triple immunolabeling study in PS hypersomniac rats. We showed that the MCH neurons activated during PS are part of both subpopulations since we found CART and non-CART MCH-activated neurons. Based on these results and the literature, we propose that MCH could be involved in memory processes and in the inhibition of muscle tone during PS.

Total recovery after bilateral paramedian thalamic infarct.

Bilateral paramedian thalamic infarcts are characterised initially by the association of acute vigilance disorders and vertical gaze palsy, followed by persisting dementia with severe mnemic disturbance, global aspontaneity and apathy. We describe a patient with a dramatic neuropsychological recovery, confirmed by testing examination and completed by a cerebral metabolism study. The pathophysiology of this type of cognitive deficit is discussed.

Multiple system degeneration and involving thalamus, reticular formation, pallido-nigral, pallido-luysian and dentato-rubral systems. A case report.

An autopsy case of multiple system degeneration is characterized by the following; (1) progressive dementia and abnormal sleep patterns, followed by Parkinsonian symptoms with terminal akinetic mutism; (2) severe symmetrical degeneration in the thalamus, particularly nucl. medialis thalami, the reticular formation of the brain stem, also the pallidonigral, pallido-Luysian and dentato-rubral systems. As far as we known, there is no case in the literature, of combined system degeneration, which shows such a wide anatomical range of lesions as the present one. Clinico-pathological correlation between dementia and degeneration of the thalamus, and between abnormal sleep-consciousness mechanism and degeneration of the reticular formation are discussed. The extrapyramidal symptoms are discussed from the clinico-pathological aspect. In addition, peculiar eosinophilic bodies are described, which were most frequently found in the putamen.