Genetic Myelopathies.

OBJECTIVE: This article provides an overview of genetic myelopathies, a diverse group of inherited, degenerative conditions that may be broadly categorized as motor neuron disorders, disorders of spinocerebellar degeneration, leukodystrophies, and hereditary spastic paraplegia. Clinical examples from each category are provided to illustrate the spectrum of genetic myelopathies and their distinguishing features that aid in differentiating genetic myelopathies from potentially treatable acquired causes of myelopathy. LATEST DEVELOPMENTS: Advances in genetic testing have vastly enhanced current knowledge of genetic myelopathies and the ability to diagnose and provide appropriate counseling to patients and their families. However, potential health care disparities in access to genetic testing is a topic that must be further explored. Although treatment for most of these conditions is typically supportive, there have been recent therapeutic breakthroughs in treatments for amyotrophic lateral sclerosis, spinal muscular atrophy, and Friedreich ataxia. ESSENTIAL POINTS: Genetic myelopathies may present with chronic and progressive symptoms, a family history of similar symptoms, and involvement of other structures outside of the spinal cord. Imaging often shows spinal cord atrophy, but cord signal change is rare. Exclusion of reversible causes of myelopathy is a key step in the diagnosis. There are many different causes of genetic myelopathies, and in some cases, symptoms may overlap, which underscores the utility of genetic testing in confirming the precise underlying neurologic condition.

Cancer and Peripheral Nerve Disease.

Patients with cancer may experience neuropathy at any stage of malignancy, ranging from symptoms that are the earliest signs of cancer to side effects of treatment. Peripheral nerves are affected most commonly in a symmetric, stocking-glove pattern. Sensory neuronopathies, plexopathies, and radiculopathies may also be seen. The most common type of neuropathy in patients with cancer is related to chemotherapy, and recently peripheral nerve complications have been described as an effect of immune checkpoint inhibitors too. Other causes include paraneoplastic syndromes, direct tumor infiltration, and radiation. Treatment focuses on addressing the underlying cancer and management of neuropathic pain.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP): Clinical Features, Diagnosis, and Current Treatment Strategies.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder characterized by weakness and sensory deficits that can lead to significant neurological disability. The diagnosis is based on a combination of clinical examination findings, electrodiagnostic studies, and other supportive evidence. Recognizing CIDP and distinguishing it from other chronic polyneuropathies is important because many patients with CIDP are highly responsive to treatment with immunosuppressive or immunomodulatory therapies. This review summarizes the clinical features, diagnosis, and current treatment strategies for CIDP. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

Median nerve penetration by a persistent median artery and vein mimicking carpal tunnel syndrome.

INTRODUCTION: Carpal tunnel syndrome (CTS) is a common clinical syndrome seen in the outpatient setting that is easily confirmed by electrodiagnostic testing. METHODS: We describe the case of a patient who presented with the classic symptoms and neurological examination for CTS, but had a normal nerve conduction study and electromyogram. RESULTS: Neuromuscular ultrasound of the median nerve on the symptomatic side revealed penetration of the nerve by a persistent median artery and vein in the mid-forearm, with a positive sonographic Tinel sign over this spot. This finding is an anatomical variation that has been described sparingly in the literature, mostly in cadavers. It has not been reported previously to be a mimic of CTS. CONCLUSIONS: This case demonstrates the diagnostic utility of neuromuscular ultrasound and the importance of considering an anatomical variation involving the median nerve in the differential diagnosis of CTS.

Understanding the etiology and management of HIV-associated peripheral neuropathy.

HIV may cause several forms of peripheral neuropathy, the most common of which is distal symmetric polyneuropathy (DSP) characterized by pain and sensory deficits in a stocking-glove distribution. The pathophysiology of DSP remains largely unknown but is thought to be related both to the neurotoxicity of HIV-through indirect immunomodulatory mechanisms-and to the neurotoxic effects of anti-retroviral therapies, most notably the dideoxynucleoside reverse transcription inhibitors or so-called d-drugs. Determining whether symptoms arise from the virus or the treatment poses a challenge to the clinician who must decide if a patient's HAART regimen should be altered. Treatment of symptoms related to HIV-DSP is a difficult task and there is no evidence that the traditional agents used in chronic neuropathic pain are efficacious in the HIV-DSP population. Indeed few pharmacologic agents have proven efficacy in HIV-DSP - these include cannabis and the capsaicin 8 % dermal patch. As such, alternative, non-pharmacologic therapies are being investigated. More research is needed to further elucidate the complex pathophysiology of HIV-DSP which may yield additional therapies for these patients.

Calciphylaxis in a dialysis patient diagnosed by muscle biopsy.

Calciphylaxis is a rare condition seen mostly in patients with chronic renal disease and secondary hyperparathyroidism who develop painful skin lesions and myopathy secondary to extensive small vessel calcification, which leads to tissue ischemia. It is typically diagnosed by a biopsy of prominent skin lesions. Here, we report a 49-year-old man with end-stage renal disease on chronic peritoneal dialysis who presented with weakness, myalgias, and necrotic skin lesions. Multiple skin biopsies were nondiagnostic because of severe extensive necrosis, and the diagnosis of systemic calciphylaxis was eventually made by a muscle biopsy. This case demonstrates the significant muscle involvement in calciphylaxis and highlights the importance of maintaining a high clinical suspicion for patients with risk factors for calciphylaxis, even when skin biopsy does not confirm it.

Scale-dependent loss of global form perception in strabismic amblyopia.

Amblyopic humans are known to have a range of spatial vision abnormalities. Prior studies have documented amblyopic deficits in global form perception but have typically used only one set of stimulus parameters. Our aim in this study was to examine the extent and nature of global form perception deficits in strabismic amblyopia using a range of spatial scales and pattern types. Glass patterns are random dot stimuli in which the local orientations of paired dots must be integrated over space to yield a global form percept. We measured coherence thresholds for discrimination of pattern structure in translational (linear) and concentric Glass patterns at three spatial scales in two control and six amblyopic observers. We found that sensitivity to Glass patterns depended on both spatial scale and pattern type in all observers. Participants with a history of abnormal early visual experience showed greater interocular threshold difference when the discrimination was based on translational patterns than when it was based on concentric patterns, and the degree of amblyopic loss was greatest at fine spatial scale. Our results show that the nature and extent of global form vision deficits vary substantially with stimulus parameters and are greatest at fine spatial scales.

Behavioral measurement of temporal contrast sensitivity development in macaque monkeys (Macaca nemestrina).

We measured the developmental time course for temporal contrast sensitivity in macaque monkeys. The animals, aged 5 weeks to 4 years, detected an unpatterned field of light sinusoidally modulated over time at frequencies ranging from 1 to 40 Hz. Young infants showed reduced sensitivity for all frequencies, and a reduced range of detectable frequencies. Sensitivity to high and low frequencies developed at different rates, but the shape of the temporal contrast sensitivity function did not change significantly with age. Temporal contrast sensitivity matures earlier than spatial contrast sensitivity. The development of high, but not low, frequency sensitivity may be limited by maturation of the magnocellular pathway.