Francis O. Walker

Huntington’s Disease

Huntingtons disease may present at any age, but most typically manifests between the ages of 35 and 45 years as a slowly progressive neurodegenerative movement disorder with cognitive and behavioral impairment. It is an autosomal-dominant disorder that has a substantial impact on family structure and dynamics in terms of providing care for affected family members and, for the offspring of an affected parent, dealing with at-risk status. Therapy that slows the progressive neuronal dysfunction or degeneration is unavailable, so pharmacotherapy is currently aimed primarily at managing behavioral and psychiatric symptoms, and, in selected cases, controlling severe chorea. Effective intervention by clinicians is possible, however, in terms of providing patients and families with accurate information about the disease, counseling them about availability of genetic testing at specialized centers, and in giving them sound advice regarding work, driving, relationships, finances, research participation, and support groups.

Botulinum Toxin Type A Neuromuscular Blockade in the Treatment of Lower Extremity Spasticity in Cerebral Palsy: A Randomized, Double-Blind, Placebo-Controlled Trial

Increased gastrocnemius/soleus muscle tone in children with cerebral palsy may cause an equinus of the ankle. Botulinum toxin type A (BTX), a neuromuscular blocking agent, reduces muscle tone in various neuromuscular disorders. The safety and short-term efficacy of BTX injections were evaluated in a prospective, 3-month, double-blind, randomized clinical trial involving 114 children with cerebral palsy and dynamic equinus foot deformity. Outcome was determined by observational gait analysis, ankle range-of-motion measurements, and quantification of muscle denervation by nerve conduction. Patients in the BTX group demonstrated improved gait function and partial denervation of the injected muscle. No serious adverse events were reported.

EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON THE COURSE OF OSTEOARTHRITIS

To test the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) accelerate the progression of osteoarthritis by reducing synthesis of vasodilator prostaglandins, thereby diminishing joint perfusion, 105 osteoarthritis patients awaiting hip arthroplasty were treated prospectively with a strong or weak prostaglandin synthesis inhibitor, indomethacin or azapropazone, respectively. Pain and radiological joint space were monitored during the period up to arthroplasty and the condition of the excised femoral head was determined. As judged by radiological and histopathological data, the two treatment groups were at a similar pathophysiological end-point when they came to arthroplasty. In the indomethacin group the affected hips lost joint space more rapidly than did the contralateral hips, a difference not seen in the azapropazone group. The patients receiving azapropazone, who had higher concentrations of synovial vasodilator prostaglandins, took longer than the indomethacin group to reach the arthroplasty end-point. Potent inhibitors of prostaglandin synthesis may be inappropriate in the management of osteoarthritis of the hip.

Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease

Background: The vast majority of the parkin mutations previously identified have been found in individuals with juvenile or early onset PD. Previous screening of later onset PD cohorts has not identified substantial numbers of parkin mutations. Methods: Families with at least two siblings with PD were ascertained to identify genes contributing to PD susceptibility. Screening of the parkin gene, by both quantitative PCR and exon sequencing, was performed in those families with either early onset PD (age onset ≤50 years) or positive lod score with a marker in intron 7 of the parkin gene. Results: A total of 25 different mutations in the parkin gene were identified in 103 individuals from 47 families. Mutations were found in both parkin alleles in 41 of the individuals, whereas a single mutation in only one of the two parkin alleles was observed in 62 individuals. Thirty-five of the subjects (34%) with a parkin mutation had an age at onset of 60 years or above with 30 of these 35 (86%) having a detectable mutation on only one parkin allele. Few significant clinical differences were observed among the individuals with two, one, or no mutated copies of the parkin gene. Conclusion: Mutations in the parkin gene occur among individuals with PD with an older age at onset (≥60 years) who have a positive family history of the disease. In addition, the clinical findings of parkin-positive individuals are remarkably similar to those without mutations.

Ultrasound of nerve and muscle

Over the last two decades, ultrasound has developed into a useful technology for the evaluation of diseases of nerve and muscle. Since it is currently not used at by the majority of clinicians involved in diagnosis or care of patients with neuromuscular disorders, this review briefly describes the technical aspects of ultrasound and its physical principles. It relates normal muscle anatomy and movement to ultrasound images in the axial and sagittal planes and follows with a discussion of ultrasound findings in chronic muscle disease. These include evident atrophy and the loss of the hypoechoic architecture of normal muscle tissue. It highlights evolving uses of the technique to measure other pathologic changes in disease including altered muscle dynamics. With high-resolution instruments nerve imaging has now become standard, and the relationships of median nerve anatomy and observations of static and dynamic images from ultrasound are reviewed. Changes seen in carpal tunnel syndrome include significant increases in the cross-sectional area of the nerve just proximal to the site of compression, loss of hyperechoic intensities within nerve, and reduced mobility. Preliminary use of the technique for the study of other nerves is reviewed as well. Ultrasound is an ideal tool for the clinical and research investigation of normal and diseased nerve and muscle complementary to existing diagnostic techniques. As the technology continues to evolve, it will likely assume a more significant role in these areas as those most able to exploit its potential, clinical neurophysiologists and neuromuscular clinicians, incorporate its use at the bedside.

Cross-sectional area reference values for nerve ultrasonography.

Ultrasound allows for a non‐invasive structural assessment of nerves, muscles, and surrounding tissues, and therefore it is increasingly being used as a supplement to traditional electrodiagnostic studies. As investigators have begun to use ultrasound to explore peripheral nerves, it has become clear that conditions such as entrapment, hereditary neuropathies, acquired neuropathies, trauma, and nerve tumors result in an increase in nerve cross‐sectional area. Reference values have not been published for the cross‐sectional area of many nerves commonly studied in diseases of the peripheral nervous system, so our goal was to obtain reference values for the nerve cross‐sectional area at the following sites: radial at antecubital fossa; radial at distal spiral groove; musculocutaneous in upper arm; trunks of the brachial plexus; vagus at carotid bifurcation; sciatic in distal thigh; tibial in popliteal fossa; tibial in proximal calf; tibial at ankle; peroneal in popliteal fossa; peroneal at fibular head; and sural in distal calf. Mean cross‐sectional area, as well as side‐to‐side differences, are reported for each site, and qualitative data are provided to guide imaging at each site. The information provided in this study should serve as the starting point for quantitatively evaluating these nerve sites with ultrasound. Muscle Nerve, 2008

Significant Linkage of Parkinson Disease to Chromosome 2q36-37

Parkinson disease (PD) is the second most common neurodegenerative disorder, surpassed in frequency only by Alzheimer disease. Elsewhere we have reported linkage to chromosome 2q in a sample of sibling pairs with PD. We have now expanded our sample to include 150 families meeting our strictest diagnostic definition of verified PD. To further delineate the chromosome 2q linkage, we have performed analyses using only those pedigrees with the strongest family history of PD. Linkage analyses in this subset of 65 pedigrees generated a LOD score of 5.1, which was obtained using an autosomal dominant model of disease transmission. This result strongly suggests that variation in a gene on chromosome 2q36-37 contributes to PD susceptibility.

Evidence-based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome

Introduction: The purpose of this study was to develop an evidence‐based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). Methods: Two questions were asked: (1) What is the accuracy of median nerve cross‐sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). Results: Neuromuscular ultrasound measurement of median nerve cross‐sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B). Muscle Nerve 46: 287–293, 2012

ULTRASONOGRAPHIC SWELLING RATIO IN THE DIAGNOSIS OF ULNAR NEUROPATHY AT THE ELBOW

High‐resolution ultrasound can demonstrate focal nerve enlargement in entrapment neuropathies. We hypothesized that a ratio between the nerve cross‐sectional area at the site of maximal enlargement and at an unaffected site may improve diagnostic accuracy in ulnar neuropathy at the elbow (UNE), when compared to a single measurement at the site of maximal enlargement. Ultrasound was used to measure the cross‐sectional area of the ulnar nerve at three sites in 30 normal, healthy controls and 26 individuals with UNE. In individuals with UNE, the ratio was 2.9:1 when the site of maximal swelling was compared with a distal ulnar nerve site and 2.8:1 when compared with a proximal site. This represented a significant increase compared with the ratio of 1.1:1 for both comparisons in controls (P < 0.0001). This type of ratio may be particularly useful for assessing entrapment in those with polyneuropathy or obesity, both of which can cause diffuse nerve enlargement. Muscle Nerve, 2008

Dermatomyositis: A dermatology-based case series

BACKGROUND Dermatomyositis is associated with significant morbidity and occasional mortality. Currently there is no consensus on treatment for patients with dermatomyositis. OBJECTIVE Our purpose was to review the clinical features and response to therapy of patients with dermatomyositis and compare these data with previous series of patients with dermatomyositis/polymyositis. METHODS Clinical characteristics of 65 patients seen during a 10-year period were reviewed retrospectively. Twenty-one of these patients were enrolled in a prospective, uncontrolled study of treatment with high-dose prednisone followed by slow tapering. RESULTS Clinical features were similar to those previously described; however, muscle strength at diagnosis was on average greater in patients in this series than in patients previously reported. Malignancy was present in 5 of 43 adult patients (12%), but was not found in patients with juvenile dermatomyositis. Another connective tissue disease was present in 19% of patients. Twelve patients had dermatomyositis sine myositis. Eighteen of 21 patients (85%) in the prednisone study group had resolution of myositis. CONCLUSION Patients with dermatomyositis in this series had less active myositis at presentation, but were otherwise similar to patients with dermatomyositis/polymyositis previously reported. Treatment with high-dose daily prednisone followed by slow tapering was effective.