Erik Ensrud

Evidence-based guideline summary: Diagnosis and treatment of limb-girdle and distal dystrophies Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine

OBJECTIVE To review the current evidence and make practice recommendations regarding the diagnosis and treatment of limb-girdle muscular dystrophies (LGMDs). METHODS Systematic review and practice recommendation development using the American Academy of Neurology guideline development process. RESULTS Most LGMDs are rare, with estimated prevalences ranging from 0.07 per 100,000 to 0.43 per 100,000. The frequency of some muscular dystrophies varies based on the ethnic background of the population studied. Some LGMD subtypes have distinguishing features, including pattern of muscle involvement, cardiac abnormalities, extramuscular involvement, and muscle biopsy findings. The few published therapeutic trials were not designed to establish clinical efficacy of any treatment. PRINCIPAL RECOMMENDATIONS For patients with suspected muscular dystrophy, clinicians should use a clinical approach to guide genetic diagnosis based on clinical phenotype, inheritance pattern, and associated manifestations (Level B). Clinicians should refer newly diagnosed patients with an LGMD subtype and high risk of cardiac complications for cardiology evaluation even if they are asymptomatic from a cardiac standpoint (Level B). In patients with LGMD with a known high risk of respiratory failure, clinicians should obtain periodic pulmonary function testing (Level B). Clinicians should refer patients with muscular dystrophy to a clinic that has access to multiple specialties designed specifically to care for patients with neuromuscular disorders (Level B). Clinicians should not offer patients with LGMD gene therapy, myoblast transplantation, neutralizing antibody to myostatin, or growth hormone outside of a research study designed to determine efficacy and safety of the treatment (Level R). Detailed results and recommendations are available on the Neurology® Web site at Neurology.org.Objective: To review the current evidence and make practice recommendations regarding the diagnosis and treatment of limb-girdle muscular dystrophies (LGMDs). Methods: Systematic review and practice recommendation development using the American Academy of Neurology guideline development process. Results: Most LGMDs are rare, with estimated prevalences ranging from 0.07 per 100,000 to 0.43 per 100,000. The frequency of some muscular dystrophies varies based on the ethnic background of the population studied. Some LGMD subtypes have distinguishing features, including pattern of muscle involvement, cardiac abnormalities, extramuscular involvement, and muscle biopsy findings. The few published therapeutic trials were not designed to establish clinical efficacy of any treatment. Principal recommendations: For patients with suspected muscular dystrophy, clinicians should use a clinical approach to guide genetic diagnosis based on clinical phenotype, inheritance pattern, and associated manifestations (Level B). Clinicians should refer newly diagnosed patients with an LGMD subtype and high risk of cardiac complications for cardiology evaluation even if they are asymptomatic from a cardiac standpoint (Level B). In patients with LGMD with a known high risk of respiratory failure, clinicians should obtain periodic pulmonary function testing (Level B). Clinicians should refer patients with muscular dystrophy to a clinic that has access to multiple specialties designed specifically to care for patients with neuromuscular disorders (Level B). Clinicians should not offer patients with LGMD gene therapy, myoblast transplantation, neutralizing antibody to myostatin, or growth hormone outside of a research study designed to determine efficacy and safety of the treatment (Level R). Detailed results and recommendations are available on the Neurology® Web site at Neurology.org.

Correspondence Regarding: TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy. J Neuropathol Exp Neurol 2010:69;918-29

We read with interest the recent article “TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy” by McKee et al (1). As neuromuscular specialists who care for large numbers of patients with amyotrophic lateral sclerosis (ALS), we have concerns about the conclusions drawn from 3 cases diagnosed as having ALS in life, while having histologic changes of both ALS and chronic traumatic encephalopathy (CTE) at autopsy. In their 12-paragraph discussion section and subsequent New York Times interview (2), the authors propose a cascade of events starting with head trauma, leading to TDP-43 proteinopathy, and ultimately to various clinical phenotypes including motor neuron disease. In support of this, they state, “… of all the putative environmental risk factors, trauma to the CNS emerges as one of the strongest and most consistent contenders for initiating the molecular cascades that result in ALS.” In actuality, the data linking trauma to ALS are significantly …

Leg amyotrophic diplegia: Prevalence and pattern of weakness at us neuromuscular centers

Objective: To identify the frequency of leg amyotrophic diplegia (LAD) at a US academic center, describe the pattern of weakness, and provide comparative data from 8 additional major US academic institutions. Background: LAD is a leg onset variant of progressive muscular atrophy (PMA). LAD weakness is confined to the legs for at least 2 years, and there are no upper motor neuron signs. Design/Methods: We present a retrospective chart review of 24 patients with the LAD presentation from the University of Kansas Medical Center ( n = 8 cases) and from 8 US academic institutions (n = 16 cases). Results: Of the 318 subjects identified in the University of Kansas Medical Center Neuromuscular Research Database, 82% (260 subjects) had amyotrophic lateral sclerosis (ALS), 1.9% (6) had familial ALS, 6.6% (21) had primary lateral sclerosis, and 9.2% (29) had lower motor neuron (LMN) disease. Of these 29 cases, 16 had PMA, 5 had brachial amyotrophic diplegia, while 8 had LAD. The mean LAD age of onset was 58 years with a male/female ratio of 3/1. Onset was asymmetric in 7/8. We identified a pelviperoneal pattern of weakness (sparing of knee extension and/or ankle plantar flexion) in 4 cases and distal predominant weakness in 3 cases. All patients had electrodiagnostic findings consistent with motor neuron disease confined to the lower extremities. We present LAD disease duration and survival data from 8 major academic neuromuscular centers. At last follow-up, weakness progressed to involve the arms in 6/24 LAD cases and of these 6 cases, 2 patients died from progression to typical ALS. From onset of symptoms, mean survival in LAD is 87 months, with 92% of cases being alive. Conclusions/Relevance: The natural history of LAD differs from typical forms of ALS and PMA. LAD is a slowly progressive disorder that accounts for a fourth of LMN disease cases. An asymmetric pelviperoneal pattern of weakness should heighten the suspicion for LAD.

Fahr’s disease

A 54 year-old man with a history of bipolar disorder presented to the neurology clinic with a two-year history of tremor affecting both hands that was worse on action. He also complained of being “slow moving” for many years. There was no family history of tremor or other movement disorders. On examination, his verbal responses were slow and he had impaired short-term memory. Glabellar …

High-frequency chest wall oscillation therapy in amyotrophic lateral sclerosis

Objectives: To evaluate the effectiveness of high-frequency chest wall oscillation (HFCWO) therapy in patients with amyotrophic lateral sclerosis (ALS). Methods: A retrospective chart review was performed of 18 patients receiving HFCWO therapy. Data was obtained pre-treatment and post-treatment including ALS Functional Rating Scale-Revised (ALSFRS-R), forced vital capacity (FVC), maximal inspiratory pressure (MIP), peak cough expiratory flow (PCEF), and daytime oximetry. Results: Daytime oximetry increased for 8 of 18 patients. None of the other measures changed significantly over the 3 months, although the change in slope of FVC, MIP, and PCEF following initiation of treatment suggested a reduction in the rate of decline of each measure. A patient survey revealed that 92% felt better after therapy and that their breathing was easier. Of patients, 85% agreed that it was easier to clear airways and that it had improved their quality of life. Conclusions: HFCWO appears to be an effective tool for airway secretion management in ALS patients and may also have an impact in improving daytime oxygen saturation.

Teaching Video NeuroImages: The elusive L5 reflex

A 61-year-old man with a history of type 2 diabetes, obesity, and lower back pain had acute severe back pain with radiation down the right lateral-posterior …

Can computers read your mind

Being fully awake and alert but trapped in a body that is unable to move or speak must be very frightening and frustrating. This is often the situation for patients in the late stages of Lou Gehrig’s disease (amyotrophic lateral sclerosis or ALS). Now there is new hope that computers may be able to help these patients communicate by, in a way, “reading their minds.” In this issue of Neurology , Kubler et al.1 reported that four people with severe ALS were able to learn to direct a computer screen cursor by modifying their brain waves through the use of a brain-computer interface (BCI). ALS is a rare disease that affects the ability to move and communicate as we usually do with speaking, gestures, and writing. More information about ALS can be found on the next page. A BCI is a computer device that helps a person operate a computer by using systems that measure brain waves rather than using his or her hands. Changes in the brain waves are then converted to systems such as a simple word-processing program. Brain waves are patterns of electrical brain activity. Brain cells can communicate with each other by electricity and chemicals called neurotransmitters. The electrical activity of the brain is measured by a test called the electroencephalogram (EEG). For this test, tiny metal discs called electrodes are painlessly stuck to the scalp with gel or paste. These electrodes can pick up the …

Aerobic exercise in muscular dystrophy Gain without pain

One of the first questions patients and families ask when diagnosed with a neuromuscular disorder is “Will exercise help or hurt?” This query is understandable given the multiple historical examples of exercise overcoming weakness and building strength, dating back to Milo of Croton in the 6th century, who practiced the progressive resistance of lifting his growing bull calf, up through more contemporary media proponents as Charles Atlas, Jane Fonda, and Tony Horton in the ubiquitous P90X infomercials. Until recently, however, definitive answers to this query have been elusive, with little hard data on which to base advice. Traditionally, patients with peripheral nerve and muscle disorders were often advised to reduce their physical activity in order to preserve their limited motor function for activities of daily living. Patients with acute radiculopathies, for example, were often admitted to inpatient services for extended bed rest as standard treatment.

Tongue infarction due to giant cell arteritis

A 78-year-old woman presented with a painful tongue ulcer and a 6-week history of temporal headaches and jaw claudication. She subsequently developed sudden vision loss in the right eye. Her erythrocyte sedimentation rate was elevated at 94 mm/1st hour (<30). We started her on corticosteroid treatment, and a temporal artery biopsy confirmed a diagnosis of giant cell arteritis. Biopsy of the tongue lesion showed inflammation of the submucosa and skeletal muscle, without evidence of …