Other Neurologic Disorders Associated with Gastrointestinal Disease

Bariatric Surgery

The increasing prevalence of obesity worldwide has led to immense growth in bariatric surgery, which typically is performed after behavioral modification, medical nutrition therapy, and physical activity enhancement strategies have failed. The number of bariatric operations performed in the United States has increased over the past three decades, and the American Society for Metabolic and Bariatric Surgery estimates that up to 228,000 procedures were performed in 2017 alone. Different methods of surgical intervention, including gastric restriction procedures (e.g., laparoscopic adjustable gastric banding, sleeve gastrectomy, vertical banded gastroplasty), malabsorptive procedures (e.g., biliopancreatic diversion, jejunoileal bypass), and combined restrictive and malabsorptive procedures (e.g., Roux-en-Y gastric bypass, duodenal switch with biliopancreatic diversion) have been performed frequently, but sleeve gastrectomy, in which approximately 75 to 85 percent of the stomach is removed along the greater curvature, is particularly growing in popularity. Neurologic complications may occur following all of these procedures, both in the immediate perioperative period and months to years after the surgery.

Neurologic complications occur in a range of 3 to 16 percent following these procedures. Although peripheral nervous system disorders appear to be the most frequent neurologic complications, encephalopathy, myelopathy, and optic neuropathy all have been reported. The mechanisms of neural injury following bariatric surgery include both mechanical compression and entrapment leading to mononeuropathies as well as nutritional deficiencies. Rapid weight loss can lead to loss of protective fat pad and compression through loss of subcutaneous tissue. Injury from mechanical retractors or malpositioning during surgery can lead to immediate complications after bariatric surgery. The most important factors in the pathogenesis of neurologic complications are nutritional deficiencies, often due to malabsorption or prolonged emesis.

Three patterns of peripheral neuropathy have been described following bariatric surgery: sensory-predominant polyneuropathy, mononeuropathy, and radicular or plexus neuropathy. Peripheral neuropathy is reported in over 15 percent of patients following bariatric surgery, compared with only 3 percent of patients undergoing cholecystectomy. In a subsequent cohort drawn from a single tertiary referral center, investigators noted peripheral neuropathy in only 7 percent but did not report on the frequency of other types of neurologic complications. Peripheral neuropathy typically is chronic, although acute inflammatory demyelinating polyneuropathy also has been reported. Carpal tunnel syndrome is the most frequent mononeuropathy, accounting for 80 percent of cases. Lateral femoral cutaneous neuropathy (meralgia paresthetica) develops in only around 1 percent of individuals despite recent weight loss being a well-known risk factor for its development. Peroneal neuropathy leading to numbness and weakness in the affected leg can manifest as “foot drop” and pose functional limitations to the patient. Risk factors include marked weight loss, rapid rate of weight loss, and postoperative complications.

Nutritional deficiencies (see Chapter 15 ) due to malabsorption are responsible for the development of neuropathy in many, although not all, instances. Deficiencies of riboflavin, pyridoxine, vitamin B ₁₂ , folate, vitamin D, vitamin E, and copper all have been described. Thiamine deficiency, one of the most common and serious complications of bariatric surgery, can lead to Wernicke encephalopathy and may appear within days to weeks following the surgery.

Optic neuropathy after bariatric surgery can be caused by copper, vitamin B ₁₂ , and thiamine deficiency. Other neuro-ophthalmic presentations are nyctalopia (the inability to see in dim light or at night) due to vitamin A or zinc deficiency and ophthalmoparesis due to vitamin E deficiency.

Muscle weakness has been reported in around 7 percent of patients after bariatric surgery, primarily in patients with hypokalemia or with global protein, vitamin D, or copper deficiencies. Postoperative rhabdomyolysis may occur and is especially frequent in patients undergoing Roux-en-Y gastric bypass; small series suggest up to three-quarters of patients may experience this complication which presents with muscle pain, typically in the gluteal region, accompanied by an increase in serum creatine kinase (CK) levels. The development of surface and deep tissue pressure during surgery may be responsible. The risk of rhabdomyolysis is greatest when the BMI of the patient is greater than 56 kg/m ² and the duration of the surgery is more than 230 minutes. CK testing should be performed in all patients after bariatric surgery to make an early diagnosis and promptly start fluids and diuretics. Osteomalacia and associated osteomalacic myopathy may also develop postoperatively. An acquired myotonic syndrome also has been reported.

Spinal cord dysfunction is another potential complication of bariatric surgery. Symptoms often start insidiously and may not become apparent until 5 to 10 years later. These symptoms may include gait ataxia and spasticity with pyramidal signs, paresthesias, loss of proprioception and vibratory sensation, and limb weakness often restricted to the legs. Many of these patients are found to have low serum vitamin B ₁₂ , vitamin E, or copper levels.

Cortical dysfunction bearing the characteristics of Wernicke encephalopathy, also known as “bariatric beriberi,” complicated bariatric surgery in approximately one-quarter of patients in one study but was noted much less frequently in larger prospective investigations. Current guidelines for bariatric surgery recommend preventive thiamine supplementation (12 mg) in multivitamin treatment for all patients undergoing surgery, with higher doses for patients with suspected deficiency.

Celiac Disease

Celiac disease (CD) is characterized by the constellation of diarrhea, malabsorption, weight loss, and gaseous distension that develops as a consequence of damage to the mucosa of the small intestine, triggered by an immune-mediated response to gluten. The prevalence of CD in American and European populations has been estimated to be approximately 1 percent, but because the number of undiagnosed patients may be considerable, its prevalence is probably much higher. Genetic factors play a role, and almost all patients with celiac disease possess specific variants of the HLA class II genes HLA-DQA1 and HLA-DQB1 that, together, encode the two chains (α and β) of the celiac-associated heterodimer proteins DQ2 and DQ8 that are expressed on the surface of antigen-presenting cells.

In recent years there has been a rise in the overall prevalence of CD in Western countries, but the reason for this “epidemic” remains unclear. The increased rate of diagnosis seems to be due to a true rise in incidence rather than merely increased awareness and detection. Approximately 30 percent of the general population carry the HLA-DQ2/8 celiac disease susceptibility genes; however, only 2 to 5 percent of these individuals will go on to develop celiac disease, suggesting that additional environmental factors contribute to disease development. Epidemiologic, clinical, and animal studies suggest that exposure to nonpathogenic microorganisms early in life is associated with a reduced risk of developing CD. Several studies have shown an association between alteration in gut microbiota composition and function and CD, some of which can precede the onset of disease and persist when patients are on a gluten-free diet.

Individuals with classic CD have serum antigliadin antibodies along with additional gliadin-related antibodies (e.g., antiendomysial, antitransglutaminase). The pathology of CD extends beyond the GI tract, leading to proposals that the term gluten sensitivity be used for individuals displaying more widespread involvement, with the label CD reserved for those with evidence of enteropathy on small bowel biopsy.

Neurologic dysfunction has been reported in 6 to 12 percent of patients with CD. A systematic review reported the prevalence of neuropathy in CD patients to be up to 39 percent, with an increased risk in older and female patients. In studies of CD patients with neurologic manifestations, gluten ataxia was reported in 20 to 40 percent of patients. Neurologic dysfunction in CD often is ascribed to nutritional deficiency secondary to malabsorption, although immunologic mechanisms may be an alternative explanation in some instances.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic or relapsing immune activation in the GI tract resulting in inflammation. Ulcerative colitis and Crohn disease are two major forms of IBD. These two conditions share many clinical and even pathologic features, but also display important differences ( Table 13-1 ). An autoimmune etiology in genetically susceptible individuals, characterized by a dysregulated mucosal immune response to antigens normally present within the intestinal lumen, is suspected in both.

In Europe and North America, the incidence of ulcerative colitis is in the range of 8 to 23 per 100,000 persons. Incidence rates of 6 to 23 per 100,000 have been reported for Crohn disease in the same regions, but in other parts of the world, such as Asia, a previously low incidence appears to be increasing.

IBD should be considered a systemic disease and involvement outside the GI tract is well described. Neurologic dysfunction appears to be relatively infrequent, with wide-ranging estimates from less than 1 to 33 percent of patients. Neurologic dysfunction may precede the appearance of GI symptoms, and both peripheral and CNS involvement occurs ( Table 13-2 ). Autoimmune mechanisms are primarily responsible for the development of neurologic involvement in IBD; however, nutritional deficiency (vitamin B ₁₂ and selenium), iatrogenic (e.g., metronidazole neurotoxicity), infection, and other processes such as thromboembolic complications may secondarily involve the nervous system. Treatment for both Crohn disease and ulcerative colitis involves potent medications, including antitumor necrosis factor α (anti-TNF-α) agents, monoclonal antibodies, and immunosuppressive medications (such as cyclosporine and sulfasalazine) that can produce neurologic complications.