Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates.

BACKGROUND: Most amyotrophic lateral sclerosis (ALS) research has focused on mice, but there are distinct differences in the functional neuroanatomy of the corticospinal pathway in primates vs. rodents. A non-human primate model may be more sensitive and more predictive for therapeutic efficacy. METHODS: Rhesus macaques received recombinant adeno-associated virus (AAV9) encoding either the ALS-related pathological protein TDP-43 or a green fluorescent protein (GFP) control by intravenous administration. Motor function and electromyography were assessed over a nine-month expression interval followed by post-mortem analyses. RESULTS: Recombinant TDP-43 or GFP was stably expressed long term. Although the TDP-43 subjects did not manifest severe paralysis and atrophy, there were trends of a partial disease state in the TDP-43 subjects relative to the control. CONCLUSIONS: These data indicate that a higher gene vector dose will likely be necessary for more robust effects, yet augur that a relevant primate model is feasible.

Neurosarcoidosis in Pediatric Patients: A Case Report and Review of Isolated and Systemic Neurosarcoidosis.

BACKGROUND: Neurosarcoidosis occurs in fewer than 5% of adults with systemic sarcoid. However, only 53 examples of neurosarcoidosis have been reported in the pediatric population, with nine of those cases being isolated neurosarcoidosis. We present the tenth case of a child with an initial presentation of isolated neurosarcoidosis and a review of the literature. METHODS: We searched the Ovid Medline database from 1946 to May 28, 2015. The Mesh terms "neurosarcoidosis," "pediatric," and "child" were exploded, and the Boolean "AND" was used to combine "neurosarcoidosis" with "pediatric" or "child." Articles that were not available in the English language were not included. RESULTS: A literature search revealed 53 children with neurosarcoidosis. The most common manifestations included cranial neuropathy (21%), papilledema or optic neuritis (15%), seizures (24.5%), and hypothalamic dysfunction (17%), with the latter two being more likely in younger children. Diagnosis is made by biopsy, but imaging and laboratory tests can aid in diagnosis. Treatment includes corticosteroids or other immunosuppressants. CONCLUSIONS: Neurosarcoidosis in children is rare, and our patient is only the tenth child with isolated neurosarcoidosis. These patients highlight the importance of considering a noninfectious diagnosis in the setting of clinical and radiographic findings suggestive of neurosarcoidosis.

Lambert-eaton myasthenic syndrome.

Lambert Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disease. Often, the signs and symptoms of LEMS are mistaken for myasthenia gravis and therefore the workup is misdirected. A physician must look for an occult malignancy when the diagnosis is made and then continue to search for a malignancy for at least 5 years after diagnosis. The diagnosis of LEMS can be confirmed with electrophysiologic studies or with serum calcium channel antibodies. In most patients with LEMS, 3,4-diaminopyridine will improve strength. In patients without malignancy, immunosuppressants do have a role in the treatment of LEMS. Patients and physicians must be aware that certain situations and drugs may exacerbate weakness.

Serial electrophysiologic studies in rhesus monkeys with Krabbe disease.

Krabbe disease is a progressive leukodystrophy that results in demyelination in the central and peripheral nervous systems in humans. It has been described in a number of mammalian species including the rhesus monkey. We performed serial nerve conduction studies beginning within the first 2 months of life in four homozygous, two heterozygous, and two normal rhesus monkeys (Macaca mulatta) to characterize the peripheral neuropathy. Mean conduction velocities of the median, ulnar, and tibial nerves were significantly slower in the affected than unaffected monkeys at all ages (P < 0.0001). The conduction velocity differences became more apparent between the affected and unaffected as the monkeys aged. When compared to the unaffected monkeys, the serial conduction velocities suggested occurrence of dysmyelination followed by demyelination in the affected monkeys. These observations provide further insight into the disease process and suggest an early window of opportunity for treating Krabbe disease.