Siblings With Mutations in TRAPPC11 Presenting With Limb-Girdle Muscular Dystrophy 2S.

Limb-girdle muscular dystrophy 2S (LGMD2S) is an autosomal recessive condition due to mutations in the TRAPPC11 gene. It is recently described with only 9 prior reported individuals. In addition to the muscular dystrophy, some affected individuals have small head size, global developmental delay, seizures, cataracts, and liver problems. Siblings with an uncharacterized LGMD were assessed; whole-exome screening revealed compound heterozygous mutations in the TRAPPC11 gene. Their presentation helps confirm the emerging phenotype for LGMD2S.

Elderly onset of weakness in facioscapulohumeral muscular dystrophy.

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

External neurolysis may result in early return of function in some muscle groups following brachial plexus surgery.

A retrospective chart review, of those individuals seen and operated on by the Multidisciplinary Brachial Plexus Clinic team at the University of Kentucky Chandler Medical Center, was undertaken to determine those individuals who had early return-of-function following surgery for BPI. Seven patients met our criteria, with four of them having substantial improvement of two or more points gained on the MRC rating scale, in one or more muscle groups within six to eight weeks after surgery. Those patients with return-of-function earlier than expected for axonal regrowth from nerve transfer or grafting, had evidence for continuity but no significant reinnervation before surgery in the muscle groups that improved. We theorize that this early improvement is related to a compression-induced dysfunction which inhibited reinnervation and was relieved by performing external neurolysis.

Sporadic Creutzfeldt-Jakob disease presenting as nonconvulsive status epilepticus case report and review of the literature.

Creutzfeldt-Jakob disease (CJD) is the most common transmissible human spongiform encephalopathy. Seizures and status epilepticus (SE) are an uncommon finding in CJD. We report a 64-year-old woman with rapid cognitive decline who had electroencephalographic (EEG) changes suggestive of nonconvulsive status epilepticus (NCSE). She was later diagnosed with sporadic CJD (sCJD). We also reviewed the literature for published cases on this topic. MEDLINE was employed to identify all published reports of CJD and SE. We identified 8 references with a total of 12 cases with CJD and NCSE. sCJD should be considered in the differential diagnosis of any patient who presents with rapid cognitive decline and EEG changes consistent with status epilepticus.

Melatonin-analog, beta-methyl-6-chloromelatonin, supplementation in spinal cord injury.

Spinal cord injury (SCI) is a devastating condition. Melatonin supplementation has been shown to lessen SCI, but its use has been limited by its side effect profile. In this work, rats underwent a moderate-to-severe contussional SCI with either placebo or beta-methyl-6-chloromelatonin, 10mg/kg or 100mg/kg supplementation. The 10mg/kg supplementation demonstrated benefit; the 100mg/kg dosage was limited by toxicity. This is the first work to assess a melatonin analog in SCI.

Exacerbation of spinal cord injury due to static compression occurring early after onset.

OBJECT: The authors used a rat model to assess spinal cord compression following an incomplete spinal cord injury (SCI). METHODS: Incomplete SCI was created in the thoracic spinal cord in a novel application of a rodent spinal cord compression model. A moderate impaction force was applied instantaneously to the spinal cord and was followed by 0 seconds, 10 seconds, 30 seconds, or 5 minutes of continued compression (termed "dwell"). The different groups were assessed by behavioral testing with the Basso, Beattie, Bresnahan locomotor rating scale, and with histological injury quantification and morphometrical analysis. RESULTS: Compression after the SCI resulted in worsened Basso, Beattie, Bresnahan scale scores; however, the duration of compression was not significant. Compression did not significantly affect the percentage of spared total tissue, percent spared total white matter, or percent spared total gray matter. Percent spared tissue at the epicenter of injury was statistically worsened by compression but not in a time-dependent manner. CONCLUSIONS: The authors' results suggest that spinal cord compression after the initial injury is an additional mechanism by which SCI worsens, and that the mechanism of this injury occurs rapidly. These data, however, do not support duration of compression as a significant variable.

Coxsackie B meningoencephalitis in a patient with acquired immunodeficiency syndrome and a multiple sclerosis-like illness.

Both Coxsackie infection and multiple sclerosis (MS) are rare in human immunodeficiency virus (HIV) infection. We report a 35-year-old woman with known HIV infection of 12 years' duration and a clinical illness of 4 years' duration consistent with MS. The latter was characterized by optic neuritis, bilateral abducens palsies, recurrent Bell's palsy, hemiparesis, and ataxia coupled with white matter abnormalities on magnetic resonance imaging (MRI). Autopsy revealed Coxsackie B meningoencephalitis; no other infectious disease were detected and no histopathological features of MS were evident. We suggest that the relapsing-remitting neurological disease in this patient was the consequence of Coxsackie B meningoencephalitis. This is the first case report, to the best of our knowledge, of an enteroviral meningoencephalitis complicating human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).

Myasthenia gravis associated with etanercept therapy.

Etanercept is an antagonist of tumor necrosis factor alpha that was developed to treat rheumatoid arthritis. In this report we present a patient who developed myasthenia gravis while taking etanercept and had resolution of symptoms after stopping it. This is the first report of this potential side effect and is of additional interest, because etanercept has been proposed as a treatment for myasthenia gravis.

Proximal sciatic nerve intraneural ganglion cyst.

Intraneural ganglion cysts are nonneoplastic, mucinous cysts within the epineurium of peripheral nerves which usually involve the peroneal nerve at the knee. A 37-year-old female presented with progressive left buttock and posterior thigh pain. Magnetic resonance imaging revealed a sciatic nerve mass at the sacral notch which was subsequently revealed to be an intraneural ganglion cyst. An intraneural ganglion cyst confined to the proximal sciatic nerve has only been reported once prior to 2009.

Gender differences in spinal cord injury are not estrogen-dependent.

Recent attention has been given to gender differences in neurotrauma, and the anecdotal suggestion is that females have better outcomes than males, suggesting that circulating levels of estrogen (E(2)) may be neuroprotective. In order to address this issue, both young adult male and ovariectomized female rats were subjected to a T10 spinal cord injury (SCI), and E2 levels were maintained at chronic, constant circulating levels. Animals were clinically evaluated for locomotor changes using the Basso-Beattie-Bresnahan (BBB) scoring system. Morphologic differences were evaluated with unbiased stereology. Data analysis failed to reveal any significant benefit for the E2 therapy in either males or females. We did find a non-estrogen-dependent difference between male and female rats in length of injury, and percent of spared tissue, with female outcomes more favorable. These results suggest that E(2) does not provide a viable therapy following SCI.

Effects of progesterone on experimental spinal cord injury.

Progesterone has been proposed to be protective to the central nervous system following injury. This study assessed progesterone supplementation in the setting of contusional spinal cord injury in male and female rats. Short-term (5 days of either 4 or 8 mg/kg progesterone) and long-term (14 days of either 8 or 16 mg/kg progesterone) therapy failed to show any significant alteration in locomotor functioning and injury morphometrics after 21 days. This study does not support progesterone as a potential therapeutic agent in spinal cord injury.

Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes.

Potassium channel mutations have been described in episodic neurological diseases. We report that K+ channel mutations cause disease phenotypes with neurodevelopmental and neurodegenerative features. In a Filipino adult-onset ataxia pedigree, the causative gene maps to 19q13, overlapping the SCA13 disease locus described in a French pedigree with childhood-onset ataxia and cognitive delay. This region contains KCNC3 (also known as Kv3.3), encoding a voltage-gated Shaw channel with enriched cerebellar expression. Sequencing revealed two missense mutations, both of which alter KCNC3 function in Xenopus laevis expression systems. KCNC3(R420H), located in the voltage-sensing domain, had no channel activity when expressed alone and had a dominant-negative effect when co-expressed with the wild-type channel. KCNC3(F448L) shifted the activation curve in the negative direction and slowed channel closing. Thus, KCNC3(R420H) and KCNC3(F448L) are expected to change the output characteristics of fast-spiking cerebellar neurons, in which KCNC channels confer capacity for high-frequency firing. Our results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases.

Phenotypic variability associated with Arg26Gln mutation in caveolin3.

Caveolin3 (CAV3) is a protein associated with dystrophin, dystrophin-associated glycoproteins, and dysferlin. Mutations in the CAV3 gene result in certain autosomal-dominant inherited diseases, namely, rippling muscle disease (RMD), limb-girdle muscular dystrophy type 1C (LGMD1C), distal myopathy, and hyperCKemia. In this report we show that a previously reported family with RMD has a mutation in the CAV3 gene. Affected individuals had either a characteristic RMD phenotype, a combination of RMD and LGMD1C phenotypes, or a LGMD1C phenotype, but one mutation carrier was asymptomatic at age 86 years. This phenotypic variability associated with mutations in CAV3 has been reported previously but only in a few families. It is important to remember the significant phenotypic variability associated with CAV3 mutations when counseling families with these mutations. These observations also suggest the presence of factors independent of the CAV3 gene locus that modify phenotype.

Traumatic brain injury increases TGF beta RII expression on endothelial cells.

Transforming growth factor beta (TGFbeta) modulates a variety of growth related functions following traumatic injury. The cellular response to TGFbeta is predominantly mediated through TGFbeta receptor I (TGFbetaRI) and receptor II (TGFbetaRII) on the cell surface and SMAD proteins intracellularly. We investigated the expression of TGFbeta receptors in the acute and chronic phases of a traumatic cerebral injury (TCI) by immunohistochemistry and in cultures of murine brain microvascular endothelial (EN) cells using cytofluorimetry. Here, we report that TGFbetaRII expression significantly increases on brain endothelial cells in the chronic phase of TCI. SMAD3 and SMAD4 protein expression were also upregulated suggesting the activation of TGFbeta receptor intracellular signaling. When TGFbetaRI and TGFbetaRII expression was studied in in vitro cultures of murine brain microvessel EN cells, TGFbetaRII showed increased expression on proliferating cells that are incorporating BrdU. These data show a differential expression of TGFbetaRI and TGFbetaRII on brain microvessel EN cells in the acute and chronic phases of TCI that might be associated with EN proliferation following injury.

Resolution of chronic inflammatory demyelinating polyneuropathy-associated central nervous system lesions after treatment with intravenous immunoglobulin.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a condition affecting the peripheral nervous system; however, it has been associated with central nervous system (CNS) involvement. The natural history and response to treatment of these CNS lesions are unknown. We report the case of a patient with CIDP which met research criteria for definite CIDP and associated symptomatic CNS lesions. She had resolution of her CNS-based clinical and radiographic findings with intravenous immunoglobulin (IVIG) therapy. IVIG is a reasonable treatment option when symptomatic, CIDP-associated CNS lesions are present.

Unilateral calf hypertrophy seen in lumbosacral stenosis: case report and review of the literature.

STUDY DESIGN: A case report of a patient with neurogenic unilateral calf hypertrophy and review of the literature are reported. OBJECTIVES: To provide further evidence that S1 radiculopathy is predisposed to develop neurogenic muscle hypertrophy. SUMMARY OF BACKGROUND DATA: Calf hypertrophy, specifically hypertrophy of the gastrocnemius muscle, is a rare but recognized presentation of S1 and less commonly L5 radiculopathies. The pathophysiology of this is incompletely understood. METHODS: We present a 59-year-old patient with painless progressive distal right leg weakness and calf enlargement. Electrodiagnostic studies and MAGNETIC RESONANCE IMAGING scanning were performed to evaluate the extent and cause of radicular damage as the etiology for unilateral calf hypertrophy. RESULTS: Examination and electrodiagnostic studies revealed right L5, right S1, and left L5 radiculopathies. Imaging studies demonstrated lumbar stenosis at L3-L4, L4-L5, and L5-S1 vertebral levels as well as L4-L5 and L5-S1 foraminal stenosis. After decompressive surgery the progressive nature of the patient's symptomatology halted, and he had partial resolution of his deficits. CONCLUSION: Although the patient had bilateral L5 radiculopathies, he only had hypertrophy in the distribution of his right S1 radiculopathy. This supports the hypothesis that dysfunction of the S1 nerve root or its distribution is a predisposing factor to develop neurogenic muscle hypertrophy. Furthermore, patients presenting with unilateral calf hypertrophy need a careful diagnostic evaluation for S1 radiculopathy as well as to exclude asymmetric presentation of systemic neuromuscular conditions.