Crohn's disease (CD) is an immune-mediated disorder that affects primarily the terminal ileum but may also affect the small and large intestines in a segmental fashion.22 The disease is more common in whites than nonwhites and is much more common in patients of Jewish descent. The incidence of CD is 2 cases per 100,000, with a prevalence of 20 to 40 per 100,000.

Clinically, CD presents as abdominal pain, diarrhea, fever, and generalized fatigue. Frequent systemic complications of CD include arthritis, ankylosing spondylitis, iritis, erythema nodosum, and pyoderma gangrenosum.22

Neurologic and psychiatric complications have been reported in up to 15% of CD patients. The most common are:22

  • seizures (the most frequent CNS complication)
  • stroke
  • peripheral neuropathy
  • myopathy
  • headache
  • depression

The increased frequency of CD in whites who are also Jewish suggests that there may be a genetic predisposition for the disorder. No markers have been clearly established. The possibility of an infectious etiology has also been extensively evaluated without any consistently identified organism.

An immune-mediated mechanism was first postulated because of the common extraintestinal manifestations and the response of the disease to immune-modulating drugs. Both immune complexes and cell-mediated immunity have been implicated in the etiology of CD, but no definitive evidence is yet available.

Neurologic manifestations

In a review of 263 patients with confirmed CD, the most common neurologic complications seen with a direct relationship to the illness included seizure, stroke, peripheral neuropathy, and myopathy, occurring in 15%.22 Other neurologic complications, including headache, cerebellar dysfunction, Parkinson's disease, optic neuritis, and sixth nerve palsy, were also seen but are not clearly related to CD.

Seizures were identified in 15 patients (5.9%). Most were generalized tonic-clonic, but partial seizures also were seen. Autoimmune phenomena, involving small vessels in the CNS, may be related to the seizures, but others have reported seizures associated with dehydration, sepsis, or metabolic disturbances.23,24

In a series of 253 patients, 12 (4.7%) had cerebral infarcts, four with bilateral subcortical infarcts. The presence of a hypercoagulable state in CD is well accepted, with evidence for increased platelet counts, coagulation factor VIII, and fibrinogen levels.25 The role of dehydration, common in CD, in addition to the hypercoagulable state, is not clearly established. Prophylactic trials with anticoagulation have not been reported, possibly because of the increased risk of bleeding from the intestinal tract in CD.

An inflammatory myopathy may be seen in as many as 1.5% of CD patients.22 This is predominantly axonal and has been reported to respond well to steroids.

Diagnosis

Extraintestinal manifestations of CD may present several years before its diagnosis.22,24,26,27 The details of a differential diagnosis are guided by the organ system primarily involved and the symptoms. When neurologic complications occur, evaluation should be guided by the nature of the specific neurologic problem.

When CNS manifestations are evident, MRI may be normal or may demonstrate nonspecific subcortical and periventricular T2 signal abnormalities. Strokes in large vessel distribution have been identified,22 as well as aseptic abscesses.24

Spinal fluid examination may reveal mildly elevated protein in cases with neuropathy and myelopathy.26 Moderately elevated cell counts (predominantly polymorphonuclear leukocytes) were seen in the presence of aseptic abscesses.24

The diagnosis of CD is most reliably made with endoscopic evaluation, biopsy, and the exclusion of other etiologies. Endoscopic examination typically reveals ulcerations in a segmental pattern, separated by normal mucosa. Pseudopolyps, strictures, and edema may be seen. Granulomas are present in 30-50% of biopsies taken from areas with active ulceration.

Treatment

The principal medical therapy of CD is anti-inflammatory agents, such as sulfasalazine or glucocorticoids. Up to 70% of patients have complications requiring surgery, including

  • bowel obstruction due to narrowing or strictures
  • symptomatic fistulae
  • persistent anal fissures or abscesses
  • intra-abdominal abscesses or perforation

Surgical therapy is not curative; relapses are frequent.28

Treatment of neurologic complications is symptomatic and includes immune-modulating drugs, when indicated. Cases of myelopathy and aseptic brain abscesses have responded to glucocorticoids or cytotoxic agents.22,24

None of the reported seizure patients required long-term therapy with antiepileptic drugs.22 In a case report of a patient with well-established CD and seizures (not clearly related to her CD), higher-than-expected dosages of phenytoin were required to maintain therapeutic levels.29 This may have resulted from increased excretion of phenytoin in the bowel, related to CD.

Prognosis

The course of CD is chronic and intermittent. Over time, it responds less well to medications, and a majority of patients require surgery at some point during the illness. Mortality from CD increases with longer duration of illness and ranges between 5% and 10%.28 Death is usually related to peritonitis or sepsis.

Seizures respond well to therapy of the underlying condition, as do the neuropathy and myelopathy. It is unclear whether immune modulation affects the hypercoagulable state in these patients, so the risk of recurrent strokes is unknown. As previously mentioned, treatment with anticoagulants may be risky in these patients, because they are predisposed to intestinal bleeding.

Adapted from: Seiden L and Krumholz A. Inflammatory noninfectious disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;135-154.
With permission from Elsevier (www.elsevier.com).

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Authored By: 
L Seiden
A Krumholz
Steven C. Schachter, MD
I<
Authored Date: 
03/2004
Reviewed By: 
Steven C. Schachter, MD
on: 
Tuesday, March 30, 2004