Physiotherapy Treatment Strategies in Axonal Type of Charcot Marie Tooth Disease: A Case Report

INTRODUCTION

Charcot-Marie-Tooth disease (CMT) includes a wide spectrum of primary inherited sensory-motor neuropathies. Diseases in this range are characterised by the degeneration of the axonal or myelin structures of the peripheral nerves, with pathological and molecular abnormalities affecting the motor and sensory neurons. CMT is a nerve-length-dependent condition marked by sensory loss, weakness in the lower extremities, diminished or missing deep tendon reflexes, and slowly increasing foot deformities, most commonly pes cavus. Most people with CMT experience symptoms in their first or second decade of life, starting with a subtle onset of weakness in their lower extremities and eventually moving up to their upper extremities.^[1]

CMTs are categorised based on their inheritance pattern and neurophysiological characteristics. Axonal CMT type 2 exhibits intact motor nerve conduction velocity (MNCV1), but demyelinating CMT type 1 is characterised by lower MNCV. CMT2A is the most common form of CMT2, making up 4–5% of all CMTs with a genetic diagnosis and roughly 10–40% of instances with axonal CMT2. The nuclear-encoded mitochondrial gene mitofusin 2 (Mfn2), which is translated into the 757-amino-acid-long protein MFN2, is linked to mutations causing CMT2A. Two nearby transmembrane segments anchor MFN2, a highly conserved GTPase, to the outer mitochondrial membrane. It is involved in controlling the balance between mitochondrial fusion and fission, two processes thought to be essential for mitochondrial quality control, cellular stress response, and apoptosis, along with its homolog Mitofusin 1 (MFN1). Early-onset, severe motor-predominant neuropathy has been linked to CMT2A, and in some cases, it is accompanied by a substantial loss of proprioception.^[2]

A systematic review conducted by Corrado et al.^[3] in April 2016 was undertaken to investigate the best available evidence to date on the rehabilitation treatment of CMT. Eleven studies were analysed, of which five examined physiotherapy treatment in CMT, while six examined the use of orthosis. The study concluded that while physiotherapy treatment is a useful tool for treating CMT, more studies are required to come up with a gold standard protocol for treatment.^[3]

CASE REPORT

A 37-year-old female, homemaker, reported to the OPD with complains of pain, frequent cramps, thinning, and weakness in both upper and lower limbs (LL>UL). She also complained of tiredness and difficulty in doing daily and household activities. She had been experiencing occasional episodes of weakness in the knees, along with a fear of falling, for the past 7 months. Due to these symptoms, she felt low and depressed.

The subject was apparently normal with no symptoms till the age of 14. On attaining puberty at the age of 14, tingling and numbness in her fingers and toes appeared. With age, she started noticing a gradual deposition of fat in her upper back, along with a gradual mild tingling of the muscles in her legs and hands. But because her symptoms were not intensifying or hindering her daily activities, she chose not to take action. After her pregnancy, there was a gradual increase in the fat deposits in the upper back, but no increase in the thinning of her hands and feet. She consulted a doctor who recommended a biopsy of the upper back. The biopsy revealed back lipomatosis.

In 2004, the patient underwent lipoma excision surgery for the upper back, but the deposition increased post-surgery and began to spread over both her arms, neck, and upper back. This was followed by thinning of the muscles in the legs, feet, and hands. Calf enlargement was also seen. By this time, the patient began experiencing fatigue in minor tasks and activities, which, coupled with changes in appearance, led to feelings of low mood and depression.

Over the course of 19 years, the patient consulted various doctors and specialists, but a proper diagnosis was not determined. In September 2023, the patient consulted a neurologist, during which she underwent various investigations, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatinine phosphokinase (CPK), peripheral smear, lactate dehydrogenase (LDH), serum acetylcholine receptor-antibody, electroneuromyography (ENMG), genetic testing, and NS. Following the tests, the diagnosis indicated CMT type 2A2B (axonal type) with characteristics suggestive of limb-girdle muscle dystrophy. Subsequently, the patient was advised to undergo physiotherapy to enhance functional status.

An initial assessment was done. The patient was conscious, awake, alert, and oriented to place and time. On observation, the patient was found to have a lean build with visible thinning of both hands and feet, and fat deposition on her upper arms and neck.

Palpation did not yield any significant abnormalities. Cranial nerve examination was found to be intact.

Sensory examination revealed that the superficial sensation of light touch in the lower limbs was impaired (Monofilament test [BASELINE- 10 g of force, 5.07 size: Subject could feel 4/10 for right lower limb and 6/10 for left lower limb). Deep reflex examination revealed that the biceps, triceps, supinator, and knee jerk had a grade 1+, and the ankle jerk had a grade 0.

Reassessment after a month and a half of treatment showed that in sensory examination, on monofilament test subject could feel 6/10 for the right lower limb and 7/10 for the left lower limb, and the ankle jerk had a value of 1+ while other reflexes remained the same.

Balance assessment found sitting dynamic to be good and standing dynamic balance to be fair.

On coordination examination, equilibrium tests of Tandem Stance and eyes closed with a narrow base of support showed moderate impairment (Grade 3); eyes closed with a wide base of support showed minimal impairment (Grade 4).

Gait analysis revealed that the subject's knees were in slight hyperextension, and weight-bearing was more on the toes. In addition to primary evaluation, assessment listed in table 1 and 2 were performed. To better grasp each framework component at a glance, the patients' difficulties were represented in the International Classification of Functioning, Disability and Health (ICF) framework.

DISSCUSSION

This case involves a 37-year-old female homemaker who presented to the outpatient department with progressive symptoms including pain, muscle cramps, thinning, and weakness in both upper and lower limbs, more pronounced in the lower limbs (LL>UL). Additionally, she reported frequent tiredness, difficulty performing daily and household activities, occasional buckling of her knees, and a fear of falling over the past 7 months. The cumulative effect of her physical symptoms led to a persistent low mood and depression, which compounded her overall functional impairment.

Like many patients with such uncommon genetic disorders, the subject went through an extended period of incorrect diagnosis and confusing clinical care. For almost twenty years, the underlying neurological diagnosis was hidden by the gradual advancement of muscular atrophy as well as intermittent periods of fat deposition.

Once the correct diagnosis was made, physiotherapy became a pivotal element of the treatment strategy for the management of her symptoms.

In a systematic review of Randomised Control Trials, it was concluded that exercises were found to improve the muscle strength of children with CMT.^[4]

Another systematic review on CMT disease noted significant effects of improvements in strength, functional activities, and physiological adaptations following exercise.^[5]

Although showing improvement in symptoms, both these reviews mentioned that well-powered studies, harmonisation of outcome measures, and clearly described interventions across studies would improve the quality and comparability of the evidence base.

The use of strength training and endurance training to improve functionality and Activities of Daily Living is supported by a systematic review conducted by Corrado et al..^[3]

In a pre- and post-intervention study on the effectiveness of an 8-week home balance training program in CMT1A, balance training exercises were shown to improve both balance and gait in patients with CMT1A.^[6]

For the subject, a physical therapy regimen was started, with an emphasis on balance training, muscular strengthening, and aerobic exercises. Exercises for strengthening the core, upper and lower limbs, balance, and gait were all included in the program. Aerobic workouts that increased in intensity gradually were offered, including stationary cycling and treadmill walking. The patient's improved scores on the Mini BEST Test Scale, Time Up and Go Test, and Fatigue Severity Scale demonstrate that, despite the degenerative nature of CMT, she made meaningful gains in her strength, balance, and functional mobility during therapy. The psychological component of the illness was also treated. Physical restrictions, social disengagement, and changed body image are common causes of emotional suffering associated with chronic conditions such as CMT.

The subject's improvement on the Hospital Anxiety and Depression Scale, showing lower scores for anxiety and despair, highlights the all-encompassing advantages of rehabilitation, which address mental and emotional health in addition to physical impairments.

However, while a significant improvement in the subject's symptoms was made, it is important to understand that CMT is a lifelong and progressive condition. Thus, a long-term management plan is required to meet the progressive needs of the patient as the disease progresses.

The subject's experience also highlights the crucial requirement for more comprehensive, statistically supported CMT rehabilitation regimens. Although significant progress has been made with the present treatment, there are still no standardised recommendations for therapy tailored to CMT. This is consistent with the results of the systematic study that was cited in the case, which showed that further investigation is required to develop a gold-standard methodology for CMT rehabilitation.

CONCLUSION

In conclusion, this study has shown that there is significant improvement in the strength, functional mobility, as well as balance and gait with exercise therapy including strength training, balance and gait training with B-TRACK protocol, and aerobic exercises for the subjects with CMT. Further research to develop a gold standard treatment protocol as well as a long-term management plan would be extremely beneficial for the future management of CMT with physiotherapy.