Inherited Neuropathies

Abstract

Inherited peripheral neuropathies are among the most common hereditary diseases of the nervous system. Charcot-Marie-Tooth (CMT) disease, also known from previous classifications as hereditary motor and sensory neuropathy (HMSN), is certainly the most common inherited neuropathy. In the past several years, various treatments for CMT have been proposed, although specific therapies are not yet available. In clinical practice, rehabilitative strategies remain the most helpful therapeutic approach to these patients. There is still a lack of consensus on the best way to rehabilitate patients affected by CMT. Based on our personal experience and on a review of the literature, we first recommend the prescription of ankle-foot orthoses (AFO) for patients affected by CMT; the choice of which patient, which AFO, and when to apply it depends on the individual condition of each patient and on the experience of the physician/therapist. Second, adaptive equipment (eg, button hook, long-handled shoehorn, elastic shoe laces) is available to compensate for hand deformities, sensory loss, and weakness. Third, moderate to intense strength training and aerobic exercise are well tolerated by patients affected by CMT; further studies are needed to establish whether these approaches are effective in improving their motor function and strength. There is not enough evidence to recommend muscle stretching exercises or proprioceptive kinesiotherapy, although in our experience both approaches may be helpful in selected CMT patients to prevent tendon retractions, muscle tightening, and loss of strength, and to improve balance. There is growing knowledge of the underlying genetic defects and molecular pathophysiology in CMT. To date, only a few clinical trials in CMT patients have been performed. A neurotrophic factor, neurotrophin 3, was used in a small sample of CMT1A patients with promising results, but it has not been tested in a larger cohort and there is currently no reason to suggest this therapy for CMT1A neuropathy. Based on positive results in an animal model of CMT1A, three trials with ascorbic acid (AA) were completed in a large number of patients with this neuropathy, with results that were negative overall. Therefore, it is not possible to recommend the use of AA in CMT1A patients at this time, but the results of a larger Italian-UK study and an American trial with higher doses of AA are still awaited. It is important to remember that a superimposed inflammatory/disimmune process may complicate the course of the neuropathy; in this case, severe worsening (especially motor) in a matter of weeks or months is a "red flag" that should suggest immunosuppressive or immunomodulatory treatment such as steroids, intravenous immunoglobulin, or plasma exchange. In fact, steroid-sensitive cases of HMSN were described many years ago, well before the genetic diagnosis was available. Symptomatic treatment to reduce neuropathic and nociceptive pain, both of which have been reported in patients affected by CMT, should be prescribed according to ...

Charcot–Marie–Tooth type 2B disease-causing RAB7A mutant proteins show altered interaction with the neuronal intermediate filament peripherin

“…Charcot–Marie–Tooth (CMT) disease is a group of genetically and clinically heterogeneous neuronal disorders [76, 79]. This neuropathy, also called hereditary motor and sensory neuropathy (HMSN), has a prevalence of 1:2,500 and its onset is usually within the first or second decade of life.…”

Current Exercise Behaviors Of Breast Cancer Patients Diagnosed With Chemotherapy-induced Peripheral Neuropathy

“…However, several studies have reported improvements in muscular strength following moderate resistance exercise programs in patients with hereditary motor and sensory neuropathies [30,31], as well as diabetic neuropathies, and those associated with fibromyalgia and chronic fatigue [32][33][34][35][36][37]. In light of these findings, many researchers recommend that exercise training serve as an important component in the comprehensive treatment plan for patients with peripheral neuropathy [33,34,38]. Moderate-to-intense strength training and aerobic exercise appears to be well tolerated by these patients [38], and is associated with improvements in motor function and nerve conduction velocity [32,35], as well as improved muscle reinnervation and increased axon regeneration [39].…”

“…In light of these findings, many researchers recommend that exercise training serve as an important component in the comprehensive treatment plan for patients with peripheral neuropathy [33,34,38]. Moderate-to-intense strength training and aerobic exercise appears to be well tolerated by these patients [38], and is associated with improvements in motor function and nerve conduction velocity [32,35], as well as improved muscle reinnervation and increased axon regeneration [39]. In addition, one investigation reported that low intensity treadmill exercise promoted Schwann cell proliferation in the injured peripheral nerve [40].…”

Charcot–Marie–Tooth disease and intracellular traffic

“…More than 30 CMT disease-causative genes are now known, allowing accurate genetic diagnosis in about 70% of patients (Table 1) (Banchs et al, 2009; Berciano, 2011; Pareyson and Marchesi, 2009; Reilly et al, 2011). Although some clinical trials are in progress, no specific treatment for CMT disease currently exists and rehabilitative strategies are presently the most helpful therapies to patients (Schenone et al, 2011). A recent trial on the use of ascorbic acid in patients affected by CMT1A, based on evidence that in transgenic mice the severity of the neuropathy is reduced by this treatment, unfortunately showed no significant effect in humans (Pareyson et al, 2011; Passage et al, 2004).…”