Spinal muscle atrophy (SMA) is an autosomal recessive disease that results in muscle weakness due to malfunction of the “survival motor neuron (SMA) gene” with loss of UMNs in the brainstem and spinal cord. The disease is classified into four forms based upon the age of onset (infantile, 0–6 months; intermediate, 6–18 months; juvenile, >18 months; and adulthood). The infantile and intermediate onset individuals have a shorter life span.

Patients present with hypotonia and absent reflexes. The limpness can be characterized as a “floppy baby syndrome.” An electromyogram will show fibrillation and muscle denervation, and genetic testing will show bi-allelic deletion of exon 7 of the SMN1 gene. Patients have developmental delay (difficulty in sitting, walking, swallowing) but no mental retardation. Poor feeding leads to a lower than normal weight. Patients develop multiple contractures. Respiratory complications (pneumonia) are the leading cause of death due to loss of strength of the pulmonary muscles and accumulation of secretions (weak cough).

There is no known cure for spinal muscular atrophy, and therefore, care is symptomatic. Because of weak spine muscles, patients develop kyphosis and scoliosis. SMA patients greatly benefit from physiotherapy. To relieve the pressure of the deformed spine on the lungs, spinal fusion may be performed in SMA patients. Once the respiratory muscles are weakened significantly, SMA patients may require BiPAP or even a tracheostomy. For difficulty in feeding, a feeding tube may be eventually required. Future treatments include gene therapy (to correct SMN gene function), stem cell therapy, and SMN gene activation.

Although the manifestations of spinal cord injury (SCI) can be severe, modern medical treatment has increased survival rates, and rehabilitation has allowed people with SCI to live active lives. In the acute phase, these patients can present with neurogenic shock secondary to the loss of sympathetic input from the brainstem to levels below the injury. There is loss of sensation, flaccid paralysis, and loss of reflexes below the level of injury. Traumatic injuries, beyond those suffered to the central nervous system (CNS), may add a component of hypovolemic shock (hypotension and bradycardia). Patients with SCI above C_3–5 require ventilatory assistance (phrenic nerve). An awake fiber-optic intubation with the head in the neutral position may be required. Succinylcholine may cause hyperkalemia if used after 48 hours of SCI (Table 35.2). For management of the acute phase, we emphasize that (1) spinal cord edema can reduce tissue perfusion and, therefore, a MAP of greater than 80 mmHg is recommended, (2) hypervolemia due to over-resuscitation can exacerbate cord edema, and (3) high-dose intravenous corticosteroids reduce cord edema and allow patients to regain function of a more distal spinal cord segment.

Patients with SCI above the 6th thoracic vertebra often develop autonomic dysreflexia/hyperreflexia in the subacute and chronic phase (Fig. 35.2). With this condition, noxious stimuli below the transection are transmitted to sympathetic fibers by spinal interneurons, which cause local vasoconstriction (dry, pale skin), catecholamine release, and hypertension. The carotid baroreceptors are stimulated which initiate a parasympathetic response from the brain causing vasodilation (sweating, flushing) and bradycardia (even cardiac dysrhythmias) above the lesion (the response cannot be transmitted down because of the transection). Therefore, the pathologic sympathetic response is unabated because there is no supraspinal input to attenuate it. Uncontrolled sympathetic stimulation causes hypertension, which may be severe and lead to headache, myocardial ischemia, cardiomyopathy, seizures, or retinal, intracerebral, or subarachnoid hemorrhages. Further, the sympathetic stimulation is amplified by hyperresponsive receptors in the denervated tissue. Denervated tissue also predisposes these patients to pressure ulcers.

These patients frequently present for urologic procedures due to bladder dysfunction and may react to urethral stimulation and bladder distention with autonomic hyperreflexia and catecholamine release. In order to block noxious stimuli below the transection, spinal anesthesia (severe hypotension may occur) or deep general anesthesia (avoid succinylcholine, hypothermia) are effective during procedures. Sustained hypertension may be treated with nitroglycerin or nitroprusside. Several studies have evaluated the effect of SCI on MAC. If the surgery is performed at the level of the lesion, MAC is unchanged. However, for surgery below the level of the SCI, MAC is reduced by 20–30 %.

Syringomyelia is the development of a fluid-filled cavity in the spinal cord (Fig. 35.3). It most commonly occurs at the cervical level and is marked clinically by neuropathic pain, numbness, weakness and muscular atrophy of the hands, and loss of temperature sensation. However, tactile sense is preserved (i.e., there is sensory dissociation). Many patients have Arnold-Chiari malformation. Treatment typically involves placement of a ventriculoperitoneal or thoracolumbar-peritoneal shunt that relieves symptoms by increasing CSF compliance. Anesthetic concerns for these patients include maintenance of spinal cord perfusion and pathologic reactions to muscle relaxants.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. It is a neurodegenerative disease of unknown etiology characterized by both UMN and LMN lesions. It often presents in the 5th–6th decade of life with fasciculations of the hands and bulbar muscles and progresses to spastic weakness of the extremities, bulbar weakness, and dysphagia. Eventually, patients lose all voluntary muscular control. Cognitive impairment is generally spared. The most common cause of death is respiratory failure due to respiratory muscle weakness, aspiration, and the inability to clear secretions. Late in the course of the disease, patients may require a feeding tube for nutrition and positive pressure ventilation to extend their life. Riluzole (Rilutek) is the only treatment that has been found to improve survival, but only to a modest extent. It may lengthen survival by several months. Anesthetic considerations for patients with ALS include autonomic dysfunction that can lead to hemodynamic instability requirement of postoperative mechanical ventilation (POMV). Succinylcholine should be avoided, and non-depolarizing muscle relaxants should be used sparingly, if at all.

Friedreich’s ataxia is a congenital disease where a trinucleotide expansion repeat causes misfolding of a mitochondrial protein that leads to degeneration of the spinocerebellar and pyramidal tracts. In addition to ataxia and spasticity, these patients may also develop paravertebral muscle weakness that can lead to kyphoscoliosis with respiratory dysfunction. Two-thirds of the patients develop hypertrophic cardiomyopathy. Classically, this disease presents shortly after birth, and patients succumb to cardiac or respiratory failure in the 3rd decade of life. The age of onset varies inversely with the number of repeats, and recently, a late onset variant has been identified.

Multiple sclerosis (MS) affects young adults between the ages of 20–40 years, being more common in women. MS is an inflammatorydisease in which the myelin sheaths (which increase the speed and efficiency of neuronal signaling) around the nerve axons are damaged, leading to demyelination and scarring. The result is plaques in demyelinated regions that manifest as paresthesias and spastic muscle weakness due to damage to nerves in the spinal cord. Symptoms and signs of MS are listed in Table 35.3. The optic nerves are often a target, leading to optic neuritis. Plaques and brain inflammation increase susceptibility to seizures. The exact cause of MS is not known, but MS is more common in families, with decreased exposure to sunlight (vitamin D deficiency), stress, smoking, low uric acid, exposure to environmental toxins, and viral infections. The natural course of the disease is one of flairs and remissions, with inflammation and hyperthermia leading to flairs, and pregnancy leading to a remission (for unclear reasons). In extreme cases, patients may experience respiratory insufficiency and dysphagia. Limb weakness may develop late in the course of the disease.

Baseline spasticity can be treated with dantrolene or baclofen, both of which can impact liver function tests and alter the pharmacokinetics of other drugs. MS patients are hypercoagulable and aggressive thromboprophylaxis should be implemented. Treatment of acute attacks includes administration of methylprednisolone, and in severe cases plasmapheresis. Other treatments include administration of interferon, mitoxantrone (immunosuppressant), natalizumab, and fingolimod. Neurorehabilitation is important for functional deficits and disability. Patients’ symptoms may be exacerbated in response to perioperative stressors, including blood pressure and temperature changes (prevent hyperthermia). The loss of upper motor neurons can lead to sensitivity to depolarizing drugs. There are case reports of spinal anesthesia exacerbating MS. One explanation for this is that demyelinated axons may be more sensitive to local anesthetic toxicity. Epidural, other regional techniques, and general anesthesia have not been implicated in MS exacerbations.

Charcot-Marie-Tooth (CMT) is a group of illnesses that are characterized by myelin deficiency (either quantitative or qualitative) that causes peripheral nerve dysfunction, with progressive muscular atrophy and loss of touch sensation. It is one of the most common inherited neuromuscular diseases. Patients suffer from muscle weakness that can cause respiratory dysfunction with increased likelihood that POMV will be required after intubation. Patients with significant muscle denervation may be hyperresponsive to depolarizing neuromuscular blocking drugs. The severity of cardiomyopathy seen in CMT patients increases with age and enhances the sensitivity to negative inotropes. Skeletal muscle deformities can be severe, resulting in difficult patient positioning or scoliosis that may reduce FVC. The loss of myelin produces the greatest impact on longer nerves, and therefore, the symptoms of the disease progress from distal to proximal. The clinical effects of a peripheral nerve block may be magnified by the preexisting neuropathology.

In the United States alone, 800,000 people suffer strokes annually and cost the economy ~$70 billion. Cerebrovascular disease (CVD) refers to both occlusive disease (i.e., carotid or vertebral artery stenosis) and potentially hemorrhagic lesions, including intracranial aneurysms and arteriovenous malformations (Fig. 35.4). Patients often have a history of transient ischemic attacks (TIAs), which are defined as transient neurological impairment lasting less than 24 h, with no residual neurological impairment.