E. Peter Bosch

Proteolipid protein is necessary in peripheral as well as central myelin

Alternative products of the proteolipid protein gene (PLP), proteolipid protein (PLP) and DM20, are major components of compact myelin in the central nervous system, but quantitatively minor constituents of Schwann cells. A family with a null allele of PLP has a less severe CNS phenotype than those with other types of PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating peripheral neuropathy, not seen with other PLP mutations of humans or animals. Direct analysis of normal peripheral nerve demonstrates that PLP is localized to compact myelin. This and the clinical and pathologic observations of the PLP null phenotype indicate that PLP/DM20 is necessary for proper myelin function both in the central and peripheral nervous systems.

Symptoms of 100 patients with electromyographically verified carpal tunnel syndrome

To determine the symptoms of carpal tunnel syndrome (CTS), screening evaluations were performed in 244 consecutive patients with sensory symptoms in the hand and unequivocal slowing of median nerve conduction at the wrist. This yielded 100 patients thought to have no explanation other than CTS for their upper limb complaints. These patients completed a hand symptom diagram (HSD) and questionnaire (HSQ) about their symptoms. CTS symptoms were most commonly reported in median and ulnar digits, followed by median digits only and a glove distribution. Unusual sensory patterns were reported by some patients. Based on the HSQ, paresthesias or pain proximal to the wrist occurred in 36.5% of hands. The usefulness of the HSD and HSQ for diagnosis was determined by asking three physicians, blinded to the diagnosis, to rate the likelihood of CTS in the patients with CTS and in 50 patients with other causes of upper extremity paresthesia. The sensitivities of the instruments ranged from 54.1% to 85.5%. Combining the HSD and HSQ ratings increased the range of sensitivities to 79.3% to 93.7%.

Peripheral neuropathies associated with monoclonal proteins

Peripheral neuropathies associated with monoclonal proteins have received considerable attention as a clinically important group of chronic late-onset neuropathies. When a monoclonal protein is found in patients with peripheral neuropathy of unknown cause, as occurs in 10% of such cases, usually no associated disease is discovered; hence MGUS. Less often, disorders such as multiple myeloma, AL amyloidosis, Waldenströms macroglobulinemia, osteosclerotic myeloma, and lymphoma are found. Demyelinating neuropathies associated with MGUS of all classes, but particularly IgM, Waldenströms macroglobulinemia, and osteosclerotic myeloma typically follow an indolently progressive course, and frequently respond to treatments aimed at interfering with putative underlying immune mechanisms. By contrast, axonal neuropathies associated with MGUS, multiple myeloma, and AL amyloidosis have generally shown no response to therapy. Recently, IgM monoclonal and polyclonal antibodies directed against human peripheral nerve antigens including MAG and various glycolipids such as GM1 ganglioside have been found in patients with specific neuropathy syndromes. Anti-MAG antibodies occur in predominantly sensory demyelinating neuropathies, whereas elevated titers of anti-GM1 ganglioside antibodies are associated with lower motor neuron syndromes with multifocal motor conduction block. Although the evidence for autoimmune mechanisms in some monoclonal protein-associated neuropathies is mounting, a causal connection between monoclonal proteins and these neurologic syndromes has yet to be established.

Spinal cord astrocytoma presenting as “idiopathic” intracranial hypertension

Increased intracranial pressure is rarely seen in association with spinal tumors. We describe a young, non-obese man who presented with increased intracranial pressure, papilledema and visual obscuration. Multiple cerebrospinal fluid (CSF) examinations with normal or minimally elevated CSF protein lead to the initial diagnosis of idiopathic intracranial hypertension. After a lumboperitoneal shunt placement a progressive thoracic myelopathy developed 7 months after onset of symptoms. The spinal MRI showed a low cervical-upper thoracic intramedullary tumor. Open biopsy confirmed a grade 3 fibrillary astrocytoma. The suspected mechanisms of spinal tumors causing increased intracranial pressure are reviewed as well as three other cases of spinal astrocytomas previously reported in the literature that presented with papilledema and increased intracranial pressure without hydrocephalus. This case illustrates that increased intracranial pressure may in exceptional cases of spinal tumors precede the more typical myelopathic presentation by months and mimic idiopathic intracranial hypertension.

Delayed ulnar neuropathy at the wrist following open carpal tunnel release.

Open carpal tunnel release is a common and successful treatment of median neuropathy at the wrist (carpal tunnel syndrome). We report a case of delayed ulnar neuropathy at the wrist with onset 2 months after open carpal tunnel release. Clinical findings, electrophysiological studies, magnetic resonance imaging, and surgical exploration demonstrated ulnar nerve compression at Guyons canal resulting from translocation of the carpal tunnel contents. To our knowledge, this is an unreported complication of open carpal tunnel release that merits wide appreciation. Muscle Nerve, 2005

Amyotrophic lateral sclerosis: An emerging era of collaboratie gene discovery

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS.

Superficial siderosis mimicking amyotrophic lateral sclerosis.

We report a case of superficial siderosis erroneously diagnosed as amyotrophic lateral sclerosis. The patients symptoms began 18 years prior with unilateral upper extremity weakness, fasciculations, and hyperreflexia. The patient then developed ataxia and hearing loss 15 years after his original symptoms. The magnetic resonance images revealed superficial siderosis involving the spinal cord and brain. We want to attract attention to superficial siderosis as a rare amyotrophic lateral sclerosis mimic disorder.

Probable Adult Polyglucosan Body Disease

Adult polyglucosan body disease is a clinicopathologic entity characterized by progressive upper and lower motor neuron dysfunction, sensory loss in the lower extremities, sphincter dysfunction, and occasionally dementia. Pathologically, numerous large polyglucosan bodies are noted in peripheral nerves, cerebral hemispheres, and the spinal cord, as well as in other systemic tissues. We present a case of probable adult polyglucosan body disease based on clinical history and examination, magnetic resonance images, and sural nerve biopsy findings.

Amyloid-like IgM deposition neuropathy: a distinct clinico-pathologic and proteomic profiled disorder

Some patients with immunoglobulin paraproteinemic neuropathy have intra‐nerve deposits that morphologically mimick amyloid, but do no stain with Congo red. Patients with amyloid‐like deposits were identified. The nerve amyloid‐like aggregates were studied by laser microdissection and dual mass spectrometry. Three male patients, all with IgM gammopathy, and neuropathy were identified. Follow‐up, disease duration was 5, 19, and 7 years, respectively. All had progressive asymmetric sensory‐onset distal axonal polyneuropathy with late motor involvement. Autonomic symptoms occurred in only one after 13 years of symptoms. None had clinical cardio‐renal involvement. One had skin papules with dermal amyloid‐like deposits. Endoneurial amyloid‐like deposits had granulo‐fibrillar ultrastructure. Mass spectrometry of laser‐dissected deposits identified IgM pentameric macroglobulin (heavy, light, and joining chains) without amyloid‐associated proteins including absent apolipoprotein E and serum amyloid P‐component. Amyloid‐like neuropathy has distinct clinical, pathologic, and proteomic features which expand the spectrum of IgM neuropathies. Patients have favorable survival, relative absence of autonomic features, and distinct proteomic profiles of the infiltrative protein in nerve.

Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection

Introduction: Potential benefit from stem cell treatments has more patients seeking treatment without understanding possible risks. Methods: We describe a woman who presented with progressive bilateral leg pain, numbness, and gait difficulties. A prior stroke, macular degeneration, osteoarthritis, and depression, led her to receive intrathecal neural stem cell therapy overseas 1 year before onset of symptoms. Results: Imaging showed marked enlargement of lumbosacral roots of the cauda equina, which was not seen before stem cell treatment. Electrodiagnostic studies confirmed chronic multiple lumbosacral radiculopathies. Biopsy of a lumbar dorsal sensory root showed myelinated fiber degeneration and loss, with endoneurial inflammation. The hypertrophic inflammatory cauda equina syndrome was potentially triggered by the prior intrathecal neural stem cell injection. Conclusions: Safety of intrathecal stem cell treatments is not routinely regulated in overseas stem cell facilities. We wish to bring this potential complication to the attention of health care providers. Muscle Nerve 48:831–835, 2013