Neuromuscular Disorders

The corticospinal tract and its neurons from the cerebral cortex through the spinal cord that subserve voluntary motor activity are known as the upper motor neuron.

The anterior horn cells, their motor roots, peripheral motor nerves, neuromuscular junctions, and muscles represent the lower motor neuron.

Maintenance of normal tone and coordination of agonist, antagonist, synergistic, and fixating muscle groups involve an integrated communication between the motor nuclei of the cerebral cortex, spinal cord, cerebellum, brainstem, thalamus, basal ganglia, and motor cortex of the cerebrum.

The cerebellum and basal ganglia facilitate volitional movement.

Thus a disease process affecting any of them can result in a neuromuscular disorder.

They may be genetically determined, congenital or acquired, acute or chronic, and progressive or static.

• Chromosomal abnormalities
• Cerebrum
• Cerebellum
• Brain stem
• Anterior Horn Cell
• Spinal muscular atrophy
• Poliomyelitis (natural or vaccine)
• Enteroviruses
• Peripheral Nerve
• Guillain-Barré syndrome
• Tick paralysis
• Vitamin E, B12, and B1 deficiencies
• Toxins e.g. Lead, thallium, arsenic, mercury, Hexane, Acrylamide, Organophosphates
• Diphtheria
• Collagen vascular disease
• Porphyria
• Paraneoplastic syndrome
• Drugs e.g. Amitriptyline, Dapsone, Hydralazine, Isoniazid, Nitrofurantoin, Vincristine
• Neuromuscular Junction
• Myasthenia gravis
• Botulism
• Aminoglycosides induced
• Muscular Dystrophy
• Duchenne
• Becker
• Limb girdle
• Facioscapulohumeral
• Myotonic
• Congenital structural myopathy
• Metabolic, Endocrine, and Mineral
• Glycogen storage disease II (Pompe disease)
• Carnitine metabolism abnormalities
• Mitochondrial abnormalities
• Thyroid excess or deficiency
• Cortisol excess or deficiency
• Hyperparathyroidism; calcium excess
• Potassium excess or deficiency (periodic paralysis)

In making the diagnosis of neuromuscular disorders, specific muscle enzymes such as the mm band of creatine kinase, imaging techniques such as USS, MRI as well as plain radiography, and molecular genetic markers such as dystrophin, merosin (in congenital muscular dystrophy), dystroglycans (in limb-girdle muscular dystrophy).

Electrophysiologic studies such as EMG, Nerve conduction velocity.

Others are muscle biopsy and biochemical studies.

These are a group of neuromuscular diseases occurring during infancy or early childhood.

Transmitted by an autosomal recessive gene and manifested by widespread muscular denervation and atrophy.

It is the 2nd most common hereditary neuromuscular disease after Duchenne Muscular Dystrophy.

Three forms are recognized:

1. Type I SMA or Werdnig-Hoffmann’s disease (Infantile Spinal Muscular Atrophy)
2. Type II (intermediate form)
3. Type III (juvenile form) Kugelberg-Welander’s disease.

All three forms are caused by mutations in a gene, the telomeric survival motor neuron gene (SMN1).

Clinical Manifestations of Spinal Muscular Atrophy (SMA)

Symmetrical Muscle Weakness: SMA primarily affects muscles, resulting in symmetrical weakness. The proximal part of the limbs is most extensively affected.

Muscular Atrophy: Muscles affected by SMA may also undergo atrophy. However, this atrophy is often concealed by subcutaneous fat, which is typical in infancy.

Involvement of Various Muscle Groups: SMA impacts muscles throughout the body, including those in the trunk, neck, and thorax. Notably, the diaphragm remains unaffected until the later stages of the disease.

Bulbar Muscle Involvement: As the disease progresses, involvement of bulbar musculature becomes prominent. This can lead to atrophy and fasciculation (involuntary muscle twitching) of the tongue.

Deep Tendon Reflexes: Deep tendon reflexes are markedly reduced or absent in individuals with SMA.

No Sensory Loss: Unlike some neuromuscular disorders, SMA typically does not cause sensory loss.

Intellectual Function: SMA does not lead to intellectual retardation or cognitive impairment.

Types of SMA: SMA is classified into three types:

1. Type I (Werdnig-Hoffmann's Disease - Infantile SMA): This type has an acute onset and rapid progression. Infants with Type I SMA are severely hypotonic at birth and have a very limited life expectancy, often not surviving beyond their first year.
2. Type II: Children with Type II SMA typically develop normally in the first six months of life. However, by around 18 months, they experience an arrest in their motor milestones. Some individuals with Type II SMA may exhibit upper extremity tremors, even detectable on an electrocardiogram.
3. Type III (Kugelberg-Welander's Disease - Juvenile SMA): Type III is the mildest form of SMA. Muscle weakness typically begins after 18 months of age, and in some cases, symptoms may not appear until adulthood. The progression is generally slower, and bulbar symptoms are usually absent.

Diagnosis of Spinal Muscular Atrophy (SMA)

Muscle Biopsy: Muscle biopsy can reveal classic features of denervation atrophy in individuals with SMA.

Genetic Studies: A definitive diagnosis can now be made by analyzing blood markers of the SMN gene, which is associated with SMA.

Biochemical Studies: In SMA Type I, serum creatine kinase (CK) levels are often normal but may be slightly elevated in some cases.

Neurophysiologic Studies: Electromyography (EMG) findings can help confirm the clinical diagnosis of motor neuron disease. Notably:

• The denervated muscles may contract spontaneously, leading to:
• Fibrillation: Involves single muscle fibers.
• Fasciculation: Involves entire motor units.
• A specific finding unique to SMA is spontaneous, rhythmic muscle activity at a frequency of 5 to 15 per second, which can be activated by voluntary effort.

Treatment: Currently, treatment for SMA is purely symptomatic and does not alter the disease's progression.

Active Exercise: In some cases, active exercise can help strengthen functioning muscles and improve overall mobility.

Guillain-Barré Syndrome, once considered a single entity, can now be subdivided into several diverse disease entities:

• Sporadic GBS (Acute Inflammatory Demyelinating Polyneuropathy or AIDP): The most common form, accounting for 85%-95% of cases.
• Acute Motor Sensory Axonal Neuropathy (AMSAN)
• Acute Motor Axonal Neuropathy (AMAN)
• Miller Fisher Syndrome
• Chronic Inflammatory Demyelinating Polyneuropathy

Pathology of GBS

GBS is characterized by marked segmental demyelination. It involves a mononuclear, predominantly T-lymphocytic and macrocytic inflammatory infiltration of all levels of the peripheral nervous system.

Key in Pathogenesis: Molecular Mimicry

Molecular mimicry is a concept that suggests similarity between self-antigens and bacterial antigens, allowing the development of an autoimmune process.

Clinical Manifestations of Guillain-Barré Syndrome (GBS)

• GBS can occur at any time during childhood but is most frequent between ages 4 and 9 years.
• The characteristic symptoms include:

1. Areflexia
2. Flaccidity
3. Relatively symmetric weakness starting in the legs and ascending to involve the arms, trunk, throat, and face.

The progression of GBS can be rapid, occurring in hours or days, or more gradual, over weeks. Typically, the child may experience:

• Numbness or paresthesia in the hands and feet
• A "heavy," weak feeling in the legs
• Inability to climb stairs or walk

Deep tendon reflexes are absent even when strength is relatively preserved. Objective signs of sensory loss are generally minor compared to the dramatic weakness.

GBS can progress to bulbar and respiratory insufficiency, often with signs such as:

• Dysphagia
• Facial weakness
• Respiratory failure

Respiratory function should be closely monitored. Dysfunction of autonomic nerves can lead to various symptoms, including hypertension, hypotension, orthostatic hypotension, tachycardia, urinary retention or incontinence, stool retention, and abnormal sweating, flushing, or peripheral vasoconstriction.

This polyneuropathy can be challenging to distinguish from an acute spinal cord syndrome. However, certain signs point more toward Guillain-Barré syndrome, including:

• Preservation of bowel and bladder function
• Loss of arm reflexes
• Absence of a sensory level
• Lack of spinal tenderness

The onset of paralysis typically follows a nonspecific viral infection by about 10 days. Common antecedent infections include respiratory tract infections or gastroenteritis.

Notable antecedents include:

• Campylobacter jejuni (most common bacterial antecedent of gastroenteritis preceding GBS)
• Mycoplasma pneumonia (associated with respiratory infection)
• Rabies vaccine (prepared from brain tissue and possibly contaminated with myelin antigens)
• Swine-flu influenza vaccine

Cranial nerve palsies can occur at any time during the illness, with the facial nerve being most commonly affected. Sensory functions that are frequently impaired include position sense, vibration, pain, and touch, in descending order of frequency.

Deep tendon reflexes are generally absent, although increased reflexes and extensor plantar responses may be occasionally recorded during the initial days of the illness.

Investigations for Guillain-Barré Syndrome (GBS)

• CSF Study: This is very crucial.
• Bacterial and Viral Cultures: Results of bacterial cultures are usually negative, and viral cultures rarely isolate specific viruses.
• CSF Protein Levels: The dissociation between high CSF protein and a lack of cellular response in a patient with an acute or subacute polyneuropathy is diagnostic of Guillain-Barré syndrome.
• Nerve Conduction Studies:
  • Motor Nerve Conduction Velocities: Greatly reduced.
  • Sensory Nerve Conduction Time: Often slow.
• Electromyogram (EMG): Shows evidence of acute denervation of muscle.

Course and Prognosis

• The clinical course is usually benign, and spontaneous recovery begins within 2–3 weeks.
• Most patients regain full muscular strength, although some are left with residual weakness.
• The tendon reflexes are usually the last function to recover. Bulbar and respiratory muscle involvement may lead to death if the syndrome is not recognized and treated.
• Although prognosis is generally good with the majority of children recovering completely, three clinical features are predictive of poor outcome with sequelae:
  • Cranial nerve involvement
  • Intubation
  • Maximum disability at the time of presentation
• An electrophysiologic feature of conduction block, by contrast, is predictive of good outcome.
• Some children with Guillain-Barré syndrome suffer relapse (about 7%). Patients are usually severely weak and may have a flaccid tetraplegia with or without bulbar and respiratory muscle involvement.
• Congenital Guillain-Barré syndrome is described rarely, presenting as generalized hypotonia, weakness, and areflexia in an affected neonate, fulfilling all electrophysiologic and cerebrospinal fluid (CSF) criteria, and in the absence of maternal neuromuscular disease.
• Treatment may not be required, and there is gradual improvement over the first few months and no evidence of residual disease by a year of age.

Treatment for Guillain-Barré Syndrome (GBS)

• Admission: Patients should be admitted for management.
• Intravenous Immunoglobulin (IV Ig): If available, IV Ig can be administered as a treatment option.
• Steroids: Steroids are also considered useful in some cases.
• Immunosuppressive Drugs: These may be used as alternatives for treatment.
• Interferon: Administration of interferon may be considered if available.
• Plasmapheresis: Plasmapheresis, a procedure to remove plasma from the blood, is another treatment option.
• Combined Treatment: In some patients, a combined administration of immunoglobulin and interferon has been found to be effective.
• Supportive Care: Supportive care is essential and should include:
  • Respiratory support
  • Prevention of pressure sores
  • Treatment of secondary bacterial infections
• Use of Antibiotics: It's important to note that the use of antibiotics does not alter the course of polyneuropathy, even when campylobacter jejuni is implicated.

This condition is characterized by abrupt onset of progressive weakness and sensory disturbances in the lower extremities.

It is an acute demyelinating disorder of the spinal cord that evolves in hours or days.

The incidence is 1 to 4 new cases/1 million people/year.

The age distribution shows peaks in the teens and 30s.

It may occur alone or in combination with demyelination in other portions of the nervous system.

The association of transverse myelitis and optic neuritis is Devic disease; acute demyelination throughout the neuraxis is diffuse encephalomyelitis.

Aetiologic Agents

History of preceding viral infection accompanied by fever and malaise is documented in most cases.

Additional infectious agents include Borrelia bugdoferri and Mycoplasma pneumoniae.

Viruses implicated include:

• Epstein-Barr virus
• Herpes
• Influenza
• Rubella
• Mumps
• Varicella viruses

Hypotheses

At least three hypotheses have been proposed to explain the pathogenesis of transverse myelitis:

• Cell-mediated autoimmune response
• Direct viral invasion of the spinal cord
• Autoimmune vasculitis

Clinical Features

Low back or abdominal pain and paresthesias of the legs are prominent symptoms in the early stages.

The leg muscles are weak and flaccid, and a sensory level is present, usually in the midthoracic region.

Pain, temperature, and light touch sensation are affected, but joint position and vibration sense may be preserved.

Sphincter disturbances are common, in which case catheterization of the bladder is necessary.

Fever and nuchal rigidity are present early in most cases.

The neurologic deficit evolves for 2–3 days and then plateaus, with flaccidity gradually changing to spasticity and with the concomitant development of upper motor neuron signs in the lower extremities.

Pathology

Pathologic examination of the cord shows marked softening and perivascular cuffing by lymphocytes, supporting an immunologic basis for the disorder.

Investigations

• Examination of the CSF shows moderate lymphocyte pleocytosis and a normal or slightly elevated protein level.
• MRI is always indicated in a suspected case of transverse myelitis to rule out a compressive lesion compromising the cord.
• CT scanning or MRI reveals mild fusiform swelling in the affected region.

Course/Management

• Spontaneous recovery occurs over a period of weeks or months and is complete in approximately 60% of cases.
• Residual deficits include bowel and bladder dysfunction and weakness in the lower extremities.
• Management is directed to bladder care and physiotherapy.

Treatment

• Corticosteroid use is the recommended treatment despite the absence of controlled studies.
• The recommended protocol is high-dose intravenous therapy followed by tapering doses of prednisone.

Differential Diagnoses

• Guillain-Barré syndrome
• Poliomyelitis
• Neuromyelitis optica (Devic disease)
• Spinal cord neoplasm
• Epidural abscess

The commonest hereditary muscular disease affecting all races or ethnic group.

It is characterized by progressive weakness, intellectual impairment, pseudohypertrophy of calf muscles as a result of proliferation of connective tissues of the calf muscles.

The incidence is about in 3600 live born infant boys.

It is inherited as an x-linked recessive and the gene locus is Xp 21.

There is milder variant called Becker muscular dystrophy.

In DMD, the deficiency of protein called dystrophin is absolute whereas in the Becker variant, the deficiency is relative.

Clinical Manifestations

• Mostly asymptomatic at birth although some maybe mildly hypotonic.
• Early gross motor skills are achieved at expected time, however, poor head control may be the first sign in some children.
• The facial muscles are often spared.
• Walking is often accomplished at normal age.
• However, during toddler period, they may exhibit lumbar lordosis due to hip girdle weakness.
• An early Gower sign may be seen by 3 years and it becomes fully expressed by 5 – 6 years.
• At this time, the typical waddling gait is seen.

Clinical Progression

• The relentless progression of weakness continues, and by 7 years of age, some patients are confined to a wheelchair while others may experience progressive difficulty in walking.
• The child is able to use the upper limbs for tasks like eating and writing.
• Involvement of respiratory muscles can manifest as ineffective cough, frequent pulmonary infections, decreasing respiratory reserve, and a risk of aspiration.
• The length of time a patient remains ambulatory varies greatly. Some are confined to a wheelchair by 7 years of age, while most continue to walk with increasing difficulty until around age 10 without orthopedic intervention.
• With orthotic bracing, physiotherapy, and sometimes minor surgery (e.g., Achilles tendon lengthening), most patients can walk until around age 12.

Physical Changes

• As the disease progresses, contractures typically involving the ankles, knees, hips, and elbows become apparent.
• Scoliosis is also commonly observed.
• Enlargement of the calf muscles and wasting of the thigh muscles are classic features.
• The calf muscle enlargement is caused by hypertrophy of some muscle fibers, infiltration of muscle by fat, and proliferation of collagen.
• The tongue is another common site of muscular hypertrophy, followed by muscles of the forearm.

Cardiomyopathy and Life Expectancy

• Cardiomyopathy is a constant feature of this disease, and its severity does not necessarily correlate with the degree of skeletal muscle weakness.
• Death typically occurs around 18-20 years of age and is commonly due to respiratory failure, intractable heart failure, respiratory infection, aspiration, or airway obstruction.
• In Becker muscular dystrophy, patients may remain ambulant until late adolescence.
• Onset of weakness is much later in Becker's variant, leading to a longer lifespan. Some patients with Becker's variant may live until their 40s with severe disability.

Diagnosis

• Diagnosis is based on a good history and physical examination.

1. History Taking:

A. Chief Complaint:

Begin by asking the parents or caregivers about the main reason for the visit. Common concerns might include delayed motor milestones, muscle weakness, or unusual gait.

B. Birth and Developmental History:

Gather information about the child's birth, including any complications during pregnancy or delivery.

Ask about developmental milestones, particularly focusing on motor milestones such as crawling, standing, and walking. Note any delays in achieving these milestones.

C. Family History:

Inquire about a family history of neuromuscular disorders, specifically DMD. Determine if there are affected siblings or a history of unexplained childhood deaths.

D. Symptoms and Progression:

Explore the onset of symptoms. In DMD, symptoms often become apparent in early childhood.

Ask about the progression of muscle weakness and any recent changes. Note if there is a specific pattern of muscle involvement (e.g., proximal muscles more affected than distal).

E. Mobility and Function:

Assess the child's current level of mobility. Determine if they are still able to walk or if they require mobility aids like a wheelchair.

Inquire about any challenges in daily activities, including climbing stairs, getting up from the floor, or reaching for objects.

F. Respiratory Function:

Ask about respiratory symptoms, such as shortness of breath, frequent respiratory infections, or nighttime breathing difficulties.

Determine if the child has ever needed respiratory support, such as non-invasive ventilation.

G. Cardiac Symptoms:

Inquire about any symptoms related to cardiac involvement, such as chest pain, palpitations, or swelling in the legs.

2. Physical Examination:

A. General Examination:

Start with a general assessment of the child's appearance, overall health, and vital signs.

B. Muscular Examination:

Perform a detailed assessment of the child's muscular system:

Evaluate muscle bulk, noting any atrophy or pseudohypertrophy, especially in the calf muscles.

Assess muscle strength, typically starting with proximal muscles (e.g., shoulder, hip) and then examining distal muscles (e.g., hand, foot).

Utilize the Medical Research Council (MRC) scale or another appropriate grading system to document muscle strength.

Check for the presence of the Gower sign, which is the characteristic way DMD patients use their hands and arms to rise from a sitting or lying position due to proximal muscle weakness.

C. Range of Motion:

Evaluate the child's joint range of motion, especially in the hips and ankles, as contractures may develop.

D. Gait Assessment:

Observe the child's gait, looking for signs of a waddling gait, difficulty in running, or toe-walking.

E. Cardiac Examination:

Perform a basic cardiac examination, including auscultation for heart murmurs or irregular rhythms.

F. Respiratory Assessment:

Assess respiratory function by observing for signs of respiratory distress, such as increased work of breathing or use of accessory muscles.

Listen for abnormal breath sounds.

G. Neurological Examination:

Conduct a neurological examination, focusing on cranial nerves, reflexes (e.g., patellar reflex), and sensory function.

Check for any cognitive or behavioral abnormalities.

H. Skin Examination:

Inspect the skin for any rashes, bruising, or lesions.

3. Additional Tests:

While history and physical examination provide valuable initial information, a confirmed diagnosis of DMD often requires additional tests such as serum creatine kinase (CK) levels, genetic testing (e.g., mutation analysis of the DMD gene), and muscle biopsy. These tests help confirm the diagnosis and determine the specific genetic mutation.

Investigations

• Serum creatine kinase is consistently markedly elevated even during the pre-symptomatic period and at birth.
• Muscle biopsy is diagnostic and shows characteristic changes, including the complete absence of dystrophin in DMD and grossly reduced amounts in Becker's variant.
• Prenatal diagnosis is possible as early as the 12th week of gestation by sampling chorionic villi for DNA analysis.
• A normal serum CK level is incompatible with the diagnosis of Duchenne dystrophy. However, in the terminal stages of the disease, the serum CK value may be considerably lower than it was a few years earlier due to muscle degeneration.
• Other lysosomal enzymes present in muscle, such as aldolase and aspartate aminotransferase, are also increased but are less specific.
• Electromyography (EMG) shows characteristic myopathic features but is not specific for Duchenne muscular dystrophy. No evidence of denervation is found, and motor and sensory nerve conduction velocities are normal.

Additional Notes

• Despite the X-linked recessive inheritance in Duchenne muscular dystrophy, about 30% of patients are new mutations, and the mother is not a carrier.
• The female carrier state usually shows no muscle weakness or any clinical expression of the disease, but affected girls are occasionally encountered, usually having much milder weakness than boys.
• These symptomatic girls are explained by the Lyon hypothesis in which the normal X chromosome becomes inactivated, and the one with the gene deletion is active.
• The full clinical picture of Duchenne dystrophy has occurred in several girls with Turner syndrome in whom the single X chromosome must have had the Xp21 gene deletion.

Treatment:

There is neither medical care nor a method of slowing the disease progress.

Treatment is multidisciplinary and symptomatic; directed towards cardiac decompensation, prompt treatment of pulmonary infection, ensuring good nutritional state, supervised physiotherapy.

Prednisone, prednisolone, deflazacort, or other steroids are useful in them.

Glucocorticoids decrease the rate of apoptosis or programmed cell death of myotubes during ontogenesis and theoretically may decelerate the myofiber necrosis in muscular dystrophy.

However, fluorinated steroids such as dexamethasone, triamcinolone avoided in them because these in themselves induce myopathy.

Future Therapy:

GENETIC ENGINEERING.

Myoblast transfer therapy.

• A major drawback is the requirement for immunosuppression to prevent rejection of the foreign cells.
• The results in cases without rejection phenomena have not been encouraging.

Introduction by intramuscular injection or a viral vector of a recombinant dystrophin gene.

Myotonic Dystrophy, also known as Steinert's Disease, is a genetic disorder that affects multiple organ systems.

It is caused by an expansion of the DM gene located on chromosome 19q 13. This gene encodes a protein called serine threonine kinase with numerous repeats of a cytosine-thymine-guanine (CTG) codon.

Aside from impacting skeletal muscles, it also affects smooth muscles in the alimentary tract and uterus.

Patients with Myotonic Dystrophy may experience a range of other health issues, including immunologic deficiencies, endocrine problems, cataracts, distinctive facial features, intellectual impairment, and various neurological abnormalities.

Clinical Manifestations

In infants, Myotonic Dystrophy may not be immediately evident at birth.

Characteristic physical features include an inverted V-shaped upper lip, thin cheeks, a scalloped appearance of the head, a narrow head shape, and a high-arched hard palate.

Wasting of the sternocleidomastoid muscle can give the impression of a long and thin neck.

Examination may reveal flattened thenar and hypothenar eminences, with visible grooves between the fingers due to atrophy of the dorsal interossei muscles.

Patients often experience difficulties climbing stairs and may exhibit a positive Gower sign, a characteristic way of using the hands and arms to rise from a sitting or lying position due to proximal muscle weakness.

Deep tendon reflexes remain functional.

A diagnostic test for Myotonic Dystrophy involves assessing myotonia, which is a slow relaxation of muscles after contraction, even after voluntary contraction or stimulation.

Speech difficulties and swallowing problems are common.

Constipation may occur due to the involvement of gastrointestinal muscles.

Cardiac issues, such as arrhythmias, are also observed.

Cataracts and varying degrees of intellectual impairment may be present.

The muscular weakness and atrophy progress gradually throughout childhood and adolescence, persisting into adulthood.

Myotonic Dystrophy is characterized by a genetic expansion of the CTG codon in the DM gene, which leads to a range of clinical manifestations affecting different organ systems.

Neonatal Form

A severe neonatal form of myotonic dystrophy occurs in a minority of infants born to mothers with myotonic dystrophy.

These infants may present with clubfoot deformities or more extensive congenital contractures affecting multiple joints, including the cervical spine.

Generalized hypotonia and weakness are evident from birth, with noticeable facial wasting.

Some infants require gavage feeding, and in severe cases, ventilator support may be needed due to respiratory muscle weakness or apnea.

Diaphragmatic function may be compromised, leading to respiratory difficulties.

Smooth muscle weakness can result in abdominal distention due to poor peristalsis, leading to gas accumulation in the stomach and intestines, further impairing respiration.

Unfortunately, about 75% of severely affected neonates do not survive beyond the first year of life.

Laboratory Evaluation

In severe neonatal cases, muscle biopsy reveals maturational arrest at various stages of development.

The primary diagnostic test is a DNA analysis of blood to detect the abnormal expansion of the CTG repeat, and prenatal diagnosis is also possible.

In older children with myotonic dystrophy, muscle biopsy specimens often show muscle fibers with central nuclei and selective atrophy of histochemical type I fibers, but degenerating fibers are typically limited and scattered, with little to no muscle fibrosis.

In young children with the common form of the disease, biopsy specimens may appear normal or show no myofiber necrosis.

Treatment

There is currently no specific treatment for the neonatal form of myotonic dystrophy.

A multidisciplinary approach is employed, focusing on symptomatic treatment and supportive care to address specific medical issues as they arise.

Myasthenia Gravis is a disorder of neuromuscular transmission, primarily caused by immune-mediated neuromuscular blockage.

In this condition, the release of acetylcholine into the synaptic cleft remains normal, but the postsynaptic membrane or motor end plate is less responsive than normal.

One of the key mechanisms involves a decrease in the number of acetylcholine receptors due to circulating antibodies, especially in acquired Myasthenia Gravis.

Myasthenia Gravis is generally non-hereditary, although a minority of cases are familial and follow an autosomal recessive inheritance pattern.

In childhood, three main clinical varieties are distinguished: Juvenile Myasthenia Gravis, Congenital Myasthenia Gravis, and Transient Neonatal Myasthenia Gravis.

Clinical Features

In the juvenile form, the earliest and most constant signs include ptosis (drooping eyelids) and varying degrees of weakness in the extraocular muscles.

Older children may need to use their fingers and thumb to help open their eyes, but the pupillary response to light is usually preserved.

Common symptoms also encompass dysphagia (difficulty swallowing) and facial weakness.

During early infancy, feeding difficulties are often a cardinal sign, and there may be poor head control due to weakness of head flexors.

While the initial involvement may be limited to bulbar muscles, it's important to note that the disease is systemic and can affect the hip girdle muscles and distal muscles of the hands.

Deep tendon reflexes are typically diminished but rarely lost, and rapid muscle fatigue is a characteristic feature of Myasthenia Gravis.

Patients often experience more pronounced symptoms later in the day or when fatigued compared to when they first wake up in the morning.

Transient Neonatal MG

Infants born to mothers with MG may experience respiratory insufficiency, characterized by an inability to suck well, generalized hypotonia or weakness.

These infants may exhibit minimal spontaneous activities for several days to weeks and, in some cases, require ventilator support during this period.

Once the abnormal antibodies disappear from the blood and muscle tissues, the infant regains normal strength and is not at risk of developing MG later in life.

This condition should be distinguished from the very rare congenital MG, which is not dependent on the maternal disease state and is always a permanent disorder without spontaneous remission.

Diagnosis

Electromyography (EMG) features are more specific in diagnosis than muscle biopsy. It shows a decremental response to repetitive nerve stimulation.

The motor nerve conduction velocity is typically normal, and the assay for anti-acetylcholine antibodies may yield inconsistent results.

Tensilon Test

The clinical test for MG is known as the Tensilon or Edrophonium test.

It involves the administration of short-acting cholinesterase inhibitors, usually edrophonium chloride.

During the test, ptosis and ophthalmoplegia should improve within a few seconds, and there should be an improvement in the fatigability of other muscles.

This test is typically performed in children aged 2 years and above. For children below 2 years, the use of edrophonium is not recommended; instead, prostigmine methylsulphate (neostigmine) is used.

The test can be conducted in various settings, including the emergency department, hospital ward, or a physician's office. Adequate preparation for potential complications, such as cardiac arrhythmia or cholinergic crisis, is essential.

Treatment

If the condition is mild, no treatment may be required. However, if symptoms are disturbing enough, cholinesterase inhibiting drugs are the therapeutic agents of choice. These drugs include neostigmine sulphate and pyridostigmine.

Due to the autoimmune basis of the condition, steroid therapy can also be beneficial. Thymomectomy should be considered in patients with a high titre of anti-acetylcholine receptor antibodies who are symptomatic and are less than 2 years old. Additionally, plasmapheresis and the use of immunoglobulins (Ig) have shown effectiveness.

Complications

Children with MG do not tolerate neuromuscular blocking drugs such as pancuronium and succinylcholine well.

Furthermore, certain antibiotics, especially aminoglycosides, may potentiate myasthenia gravis, especially when administered intravenously.

Prognosis

Prognosis in MG is difficult to predict. Some patients experience spontaneous remission after several months or years, while others have a permanent disease that extends into adulthood.

Immunosuppression, thymectomy, and treatment of associated conditions like hypothyroidism may provide a cure or significant improvement in symptoms.

Differential Diagnosis

When evaluating a patient with symptoms of muscle weakness and neuromuscular dysfunction, it's essential to consider differential diagnoses, which may include:

• Organophosphate poisoning
• Tick paralysis
• Botulinum poisoning

Facioscapulohumeral muscular dystrophy, also known as Landouzy-Dejerine disease, represents a group of diseases with similar clinical manifestations rather than a single disease entity.

It typically follows an autosomal dominant inheritance pattern, and genetic anticipation is often observed within affected families, with subsequent generations experiencing more severe involvement at an earlier age.

Clinical Manifestations

Facioscapulohumeral dystrophy primarily affects facial and shoulder girdle muscles, with the following notable clinical features:

• The mouth appears rounded and puckered due to protrusion of the upper and lower lips.
• Inability to close the eyes completely during sleep.
• Some patients exhibit weakness in extraocular muscles, although complete ophthalmoplegia is rare.
• Occasionally associated with Möbius syndrome.
• Pharyngeal and tongue weakness is usually less severe than facial involvement.
• Hearing loss and retinal vasculopathy may be present.
• Scapular winging is prominent, often in infants.
• Weakness and atrophy of hip girdle and thigh muscles.
• Appearance of Gowers sign and Trendelenburg gait.
• Contractures are uncommon.
• Weakening of anterior tibial and peroneal muscles can lead to footdrop, typically in advanced cases.
• Lumbar lordosis and kyphoscoliosis are common complications due to axial muscle involvement.
• Facioscapulohumeral muscular dystrophy can manifest as a mild disease with minimal disability.
• Clinical symptoms may not appear in childhood, delaying onset into middle adulthood.
• Unlike most other muscular dystrophies, asymmetry of weakness is common.

Diagnosis

Muscle biopsy plays a crucial role in distinguishing between different forms of facioscapulohumeral dystrophy (FSH dystrophy).

General histopathologic findings in muscle biopsy material include:

• Extensive proliferation of connective tissue between muscle fibers.
• Wide variation in fiber size, with many hypertrophic and atrophic myofibers.
• Scattered degenerating and regenerating fibers.

Treatment

Currently, there is no treatment available to alter the progression of FSH dystrophy. Management typically involves a multidisciplinary approach:

• Orthopedic measures may be employed to address conditions such as footdrop and scoliosis.
• Reconstructive surgery can be considered for cosmetic improvement of facial muscles of expression.