Clinical, Electrophysiological, and Serological Evaluation of Patients with Cramp-Fasciculation Syndrome.

INTRODUCTION: Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. METHODS: Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27-65 years old) were investigated. RESULTS: All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain. Antibodies to uncharacterized voltage-gated potassium channel (VGKC)-complex proteins were found in 2 patients and to contactin-associated protein-like 2 (CASPR2) in 1 patient. None of the patients had a tumor. Most of the patients revealed prolonged after-discharges following tibial nerve stimulation. Nerve conduction studies and R-R interval variability tests were normal, whereas sympathetic skin responses were increased in amplitude in 3 seronegative patients. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas 1 VGKC-antibody-positive patient was resistant to carbamazepine and immunosuppressant treatment. CONCLUSION: Neuropathic pain and VGKC-complex antibodies may be encountered in CFS patients. Although autonomic symptoms are commonly found in CFS, routine autonomic system tests which are done in electrophysiology laboratories might yield normal results.

NMDA receptor encephalitis with cancer of unknown primary origin.

PURPOSE: N-methyl-D-aspartate receptor (NMDAR) encephalitis may present as a paraneoplastic syndrome in young women and is often associated with ovarian teratoma. METHODS: We report 2 male cases of NMDAR encephalitis presenting with metastatic cancer of unknown primary origin. RESULTS: Both patients showed cognitive dysfunction as well as other neurological symptoms, slow waves on EEG, and NMDAR antibodies in sera and CSF. Symptoms were effectively treated by pulse steroid and intravenous immunoglobulin treatment. The patients developed metastatic small cell neuroendocrine carcinoma of the parotid gland and inguinal metastatic squamous cell cancer shortly after their neurological episodes. Follow-up PET studies showed small cell lung cancer in the first patient while no primary origin could be found in the second patient. CONLUSIONS: Our cases imply that NMDAR encephalitis may present with metastatic cancers that display slow progression rates and occur after encephalitis attacks.

Nerve conduction studies in Charcot-Marie-Tooth disease in a cohort from Turkey.

INTRODUCTION: In the demyelinating form of Charcot-Marie-Tooth disease, median motor conduction velocity (MCV) was noted to be around 20 m/s in peripheral myelin protein 22 (PMP22) duplications, in contrast to higher MCVs in connexin 32 gene (Cx32) mutations and lower MCVs in the demyelinating form of myelin protein zero gene (MPZ) mutations. METHODS: Nerve conduction studies were performed in 64 families with both common and rare mutations. RESULTS: Mean MCV of the median nerve was 20 ± 5 m/s in PMP22 duplications, 34 ± 6 m/s in Cx32 mutations, 20 ± 9 m/s in KIAA1985 (SH3TC2) mutations, and 11 ± 8 m/s in MPZ mutations. Conduction was generally uniform; however, conduction blocks were present in 1 patient each with the MPZ mutation and PMP22 duplication, both with unusual phenotypes. CONCLUSION: Our results confirm those of the other investigators. Electrophysiological results of the rare KIAA1985 (SH3TC2) mutation reveal that their MCVs span a broad range and that conduction is uniform.

Clinicopathological and genetic study of early-onset demyelinating neuropathy.

Autosomal recessive demyelinating Charcot-Marie-Tooth disease (CMT4), Dejerine-Sottas disease and congenital hypomyelinating neuropathy are variants of hereditary demyelinating neuropathy of infancy, a genetically heterogeneous group of disorders. To explore the spectrum of early-onset demyelinating neuropathies further, we studied the clinicopathological and genetic aspects of 20 patients born to unaffected parents. In 19 families out of 20, consanguinity between the parents or presence of an affected sib suggested autosomal recessive transmission. Screening of various genes known to be involved in CMT4 revealed six mutations of which five are novel. Four of these novel mutations occurred in the homozygous state and include: one in GDAP1, one in MTMR2, one in PRX and one in KIAA1985. One patient was heterozygous for a novel MTMR2 mutation and still another was homozygous for the founder mutation, R148X, in NDRG1. All patients tested negative for mutations in EGR2. Histopathological examination of nerve biopsy specimens showed a severe, chronic demyelinating neuropathy, with onion bulb formation, extensive demyelination of isolated fibres and axon loss. We did not discern a specific pattern of histopathology that could be correlated to mutations in a particular gene.