Celiac Disease Can Have Neurologic Presentation : Patients who have gluten ataxia improve or stabilize within a year of starting a strict gluten-free diet.

NEW YORK — Neurologic dysfunction may be the sole presenting symptom of celiac disease, according to Dr. Marios Hadjivassiliou, a neurologist at the Royal Hallamshire Hospital in Sheffield, England.

Speaking at an international symposium on celiac disease, Dr. Hadjivassiliou reported that his neurology clinic has followed 312 patients with gluten sensitivity who presented with various types of neurologic dysfunction. The majority of the patients had gluten ataxia (n = 147), while others had peripheral neuropathy (n = 116), gluten encephalopathy (n = 31), and gluten myopathies (n = 13).

His previous research has found that gluten ataxia is the single most common cause of sporadic, idiopathic ataxia—accounting for 40% of sporadic, idiopathic ataxias and 21% of all ataxias (Brain 2003;126:685–91). “These patients have limb and gait ataxia, and one-third will also have an enteropathy,” he said.

He has also shown that patients with gluten ataxia improve or stabilize within a year of starting a strict gluten-free diet, even in the absence of enteropathy (J. Neurol. Neurosurg. Psychiatry 2003;74:1221–4). “However, the sooner you intervene, the better,” he said. “About 60% of these patients will have atrophy of the cerebellum shown on MRI, and there is loss of Purkinje cells, which is not reversible.”

With regard to gluten neuropathy, new research by Dr. Hadjivassiliou has shown that it accounts for 26% of all axonal neuropathies and 34% of idiopathic, sporadic axonal neuropathies (J. Neurol. Neurosurg. Psychiatry 2006;77:1262–6). “The prevalence of gluten-sensitive enteropathy is 10 times higher in patients with axonal neuropathy compared to healthy individuals,” he said.

He has also recently published evidence showing that patients with gluten-sensitive neuropathy show improvement on a gluten-free diet, while patients who continue to ingest gluten deteriorate further (Muscle Nerve 2006;34:762–6).

However, neuropathies are still common in treated celiac patients, he added. “If you screen adults with established celiac disease, one-quarter of them will have evidence of neuropathy despite a gluten-free diet.”

Gluten encephalopathy—episodic headache often associated with confusion and focal neurologic dysfunction, requiring hospital admission—is also a neurologic manifestation of celiac disease, Dr. Hadjivassiliou reported.

Magnetic resonance imaging shows white matter abnormalities associated with focal neurologic deficits, and these are not always reversible even after the patient starts a gluten-free diet. However, the headaches respond well to the elimination of gluten, he said.

Dr. Hadjivassiliou believes that nutritional deficiencies resulting from malabsorption in the small intestine can now be ruled out as a cause of gluten-sensitive neuropathies.

“The overwhelming evidence is for an immune-mediated mechanism,” he said, adding that pathological data mainly from postmortem examinations show evidence of MRI inflammatory changes with perivascular emphasis primarily affecting the cerebellum and brainstem, but also other parts of the brain.

He urged physicians to recognize that celiac disease is a systemic disorder that has diverse manifestations in the body beyond the gastrointestinal system. “There is a historical misconception that gluten sensitivity is solely a disease of the gut,” he said. “To recognize the neurologic impact, you have to appreciate it is a systemic disorder.”

His experience is that many gluten-sensitive neurologic disorders have an age of onset in the mid-50s. Many patients have no gastrointestinal symptoms, but serologic tests for IgG and IgA antigliadin antibodies are positive.

Endomysial antibodies or tissue transglutaminase antibodies can help identify those patients who may also have an enteropathy; however, only one-third of these patients will have histologic confirmation of this on biopsy.

MRI scans taken over 7 years show progressive cerebellar degeneration in a patient with gluten ataxia who refused to go on a gluten-free diet (earliest scan at upper left to most recent at lower right). Courtesy Dr. Marios Hadjivassiliou

NEW YORK — Neurologic dysfunction may be the sole presenting symptom of celiac disease, according to Dr. Marios Hadjivassiliou, a neurologist at the Royal Hallamshire Hospital in Sheffield, England.

Speaking at an international symposium on celiac disease, Dr. Hadjivassiliou reported that his neurology clinic has followed 312 patients with gluten sensitivity who presented with various types of neurologic dysfunction. The majority of the patients had gluten ataxia (n = 147), while others had peripheral neuropathy (n = 116), gluten encephalopathy (n = 31), and gluten myopathies (n = 13).

His previous research has found that gluten ataxia is the single most common cause of sporadic, idiopathic ataxia—accounting for 40% of sporadic, idiopathic ataxias and 21% of all ataxias (Brain 2003;126:685–91). “These patients have limb and gait ataxia, and one-third will also have an enteropathy,” he said.

He has also shown that patients with gluten ataxia improve or stabilize within a year of starting a strict gluten-free diet, even in the absence of enteropathy (J. Neurol. Neurosurg. Psychiatry 2003;74:1221–4). “However, the sooner you intervene, the better,” he said. “About 60% of these patients will have atrophy of the cerebellum shown on MRI, and there is loss of Purkinje cells, which is not reversible.”

With regard to gluten neuropathy, new research by Dr. Hadjivassiliou has shown that it accounts for 26% of all axonal neuropathies and 34% of idiopathic, sporadic axonal neuropathies (J. Neurol. Neurosurg. Psychiatry 2006;77:1262–6). “The prevalence of gluten-sensitive enteropathy is 10 times higher in patients with axonal neuropathy compared to healthy individuals,” he said.

He has also recently published evidence showing that patients with gluten-sensitive neuropathy show improvement on a gluten-free diet, while patients who continue to ingest gluten deteriorate further (Muscle Nerve 2006;34:762–6).

However, neuropathies are still common in treated celiac patients, he added. “If you screen adults with established celiac disease, one-quarter of them will have evidence of neuropathy despite a gluten-free diet.”

Gluten encephalopathy—episodic headache often associated with confusion and focal neurologic dysfunction, requiring hospital admission—is also a neurologic manifestation of celiac disease, Dr. Hadjivassiliou reported.

Magnetic resonance imaging shows white matter abnormalities associated with focal neurologic deficits, and these are not always reversible even after the patient starts a gluten-free diet. However, the headaches respond well to the elimination of gluten, he said.

Dr. Hadjivassiliou believes that nutritional deficiencies resulting from malabsorption in the small intestine can now be ruled out as a cause of gluten-sensitive neuropathies.

“The overwhelming evidence is for an immune-mediated mechanism,” he said, adding that pathological data mainly from postmortem examinations show evidence of MRI inflammatory changes with perivascular emphasis primarily affecting the cerebellum and brainstem, but also other parts of the brain.

He urged physicians to recognize that celiac disease is a systemic disorder that has diverse manifestations in the body beyond the gastrointestinal system. “There is a historical misconception that gluten sensitivity is solely a disease of the gut,” he said. “To recognize the neurologic impact, you have to appreciate it is a systemic disorder.”

His experience is that many gluten-sensitive neurologic disorders have an age of onset in the mid-50s. Many patients have no gastrointestinal symptoms, but serologic tests for IgG and IgA antigliadin antibodies are positive.

Endomysial antibodies or tissue transglutaminase antibodies can help identify those patients who may also have an enteropathy; however, only one-third of these patients will have histologic confirmation of this on biopsy.

MRI scans taken over 7 years show progressive cerebellar degeneration in a patient with gluten ataxia who refused to go on a gluten-free diet (earliest scan at upper left to most recent at lower right). Courtesy Dr. Marios Hadjivassiliou

NEW YORK — Neurologic dysfunction may be the sole presenting symptom of celiac disease, according to Dr. Marios Hadjivassiliou, a neurologist at the Royal Hallamshire Hospital in Sheffield, England.

Speaking at an international symposium on celiac disease, Dr. Hadjivassiliou reported that his neurology clinic has followed 312 patients with gluten sensitivity who presented with various types of neurologic dysfunction. The majority of the patients had gluten ataxia (n = 147), while others had peripheral neuropathy (n = 116), gluten encephalopathy (n = 31), and gluten myopathies (n = 13).

His previous research has found that gluten ataxia is the single most common cause of sporadic, idiopathic ataxia—accounting for 40% of sporadic, idiopathic ataxias and 21% of all ataxias (Brain 2003;126:685–91). “These patients have limb and gait ataxia, and one-third will also have an enteropathy,” he said.

He has also shown that patients with gluten ataxia improve or stabilize within a year of starting a strict gluten-free diet, even in the absence of enteropathy (J. Neurol. Neurosurg. Psychiatry 2003;74:1221–4). “However, the sooner you intervene, the better,” he said. “About 60% of these patients will have atrophy of the cerebellum shown on MRI, and there is loss of Purkinje cells, which is not reversible.”

With regard to gluten neuropathy, new research by Dr. Hadjivassiliou has shown that it accounts for 26% of all axonal neuropathies and 34% of idiopathic, sporadic axonal neuropathies (J. Neurol. Neurosurg. Psychiatry 2006;77:1262–6). “The prevalence of gluten-sensitive enteropathy is 10 times higher in patients with axonal neuropathy compared to healthy individuals,” he said.

He has also recently published evidence showing that patients with gluten-sensitive neuropathy show improvement on a gluten-free diet, while patients who continue to ingest gluten deteriorate further (Muscle Nerve 2006;34:762–6).

However, neuropathies are still common in treated celiac patients, he added. “If you screen adults with established celiac disease, one-quarter of them will have evidence of neuropathy despite a gluten-free diet.”

Gluten encephalopathy—episodic headache often associated with confusion and focal neurologic dysfunction, requiring hospital admission—is also a neurologic manifestation of celiac disease, Dr. Hadjivassiliou reported.

Magnetic resonance imaging shows white matter abnormalities associated with focal neurologic deficits, and these are not always reversible even after the patient starts a gluten-free diet. However, the headaches respond well to the elimination of gluten, he said.

Dr. Hadjivassiliou believes that nutritional deficiencies resulting from malabsorption in the small intestine can now be ruled out as a cause of gluten-sensitive neuropathies.

“The overwhelming evidence is for an immune-mediated mechanism,” he said, adding that pathological data mainly from postmortem examinations show evidence of MRI inflammatory changes with perivascular emphasis primarily affecting the cerebellum and brainstem, but also other parts of the brain.

He urged physicians to recognize that celiac disease is a systemic disorder that has diverse manifestations in the body beyond the gastrointestinal system. “There is a historical misconception that gluten sensitivity is solely a disease of the gut,” he said. “To recognize the neurologic impact, you have to appreciate it is a systemic disorder.”

His experience is that many gluten-sensitive neurologic disorders have an age of onset in the mid-50s. Many patients have no gastrointestinal symptoms, but serologic tests for IgG and IgA antigliadin antibodies are positive.

Endomysial antibodies or tissue transglutaminase antibodies can help identify those patients who may also have an enteropathy; however, only one-third of these patients will have histologic confirmation of this on biopsy.

MRI scans taken over 7 years show progressive cerebellar degeneration in a patient with gluten ataxia who refused to go on a gluten-free diet (earliest scan at upper left to most recent at lower right). Courtesy Dr. Marios Hadjivassiliou