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Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in GLI3 and other patterning genes are involved in HH pathogenesis. About 50%-80% of children with HH have severe rage and aggression and a majority of patients exhibit externalizing disorders. Behavioral disruption and intellectual disability may predate epilepsy. Neuropsychological, sleep, and endocrine disorders are typical. The purpose of this article is to provide a summary of the current understanding of HH and to highlight opportunities for future research., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network., Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness., Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks., Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness., (© 2016 American Academy of Neurology.)

Idiopathic narcolepsy usually results from a loss of the hypothalamic neuropeptide orexin (hypocretin), but the cause of secondary narcolepsy resulting from focal brain lesions is unknown. The authors describe a young man who developed narcolepsy after a large hypothalamic stroke. His lesion included much of the hypothalamic region in which orexin is produced, and his CSF concentration of orexin was low. The authors hypothesize that a loss of orexin neurons or their relevant targets may be the specific neuropathology causing this and many other cases of secondary narcolepsy.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

The somatotopic organization of the facial nucleus and the distribution of the corticofacial projection in the monkey were studied by the use of retrograde and anterograde transport of horseradish peroxidase. Facial motor neurons innervating lower facial muscles were primarily found in the lateral part of the nucleus, those supplying upper facial muscles in the dorsal part of the nucleus, and those innervating the platysma and posterior auricular muscles in the medial part of the nucleus. Descending corticofacial fibers innervated the lower facial motor nuclear region bilaterally, although with contralateral predominance. The upper facial motor nuclear regions received scant direct cortical innervation on either side of the brain. Our results indicate that upper facial movement, like that at the shoulder, is relatively preserved in upper motor neuron palsy because these motor neurons receive little direct cortical input. By contrast, the lower facial muscles, like those of the hand, are more severely affected because their motor neurons normally depend upon significant cortical innervation.

The loss of cortical cholinergic innervation in senile dementia of the Alzheimer's type (SDAT) is associated with cell loss in the nucleus basalis and related cell groups (magnocellular basal nucleus, MBN). We examined MBN in Nissl-, acetylcholinesterase- and thioflavin S-stained sections in two cases of SDAT and in four control brains. Using these sensitive methods, senile plaques were easily demonstrated in MBN, and most MBN neurons showed neurofibrillary degeneration as an early change. Cell loss appeared to be due to maturation of neurofibrillary tangles, displacing normal cellular contents. In contrast to theories that the cell loss in MBN represents retrograde degeneration due to axonal injury in the cerebral cortex, MBN neuronal perikarya may be involved by the same primary processes as cortical neurons.

A 31-year-old woman with acute myelomonocytic leukemia presented with meningeal signs and a cerebellar mass attributed to leukemic infiltration. The mass disappeared with radiation therapy and intraventricular chemotherapy, but the patient subsequently suffered several spinal nerve root recurrences, disseminated herpes zoster, and progressive multifocal leukoencephalopathy. At autopsy, there was no trace of the meningeal leukemia or cerebellar infiltrate. This case illustrates several of the neurologic complications of acute nonlymphocytic leukemia, and raises the question whether patients with the myelomonocytic form of this disease might benefit from prophylactic central nervous system treatment.