ARTICLE IN BRIEF
Investigators proposed a new classification of adult-onset temporal lobe epilepsy with hippocampal sclerosis that may be caused by limbic encephalitis.
Some cases of adult-onset temporal lobe epilepsy-hippocampal sclerosis (TLE-HS) may be caused by autoimmune limbic encephalitis, according to German investigators who reported results of an analysis of MRI, clinical symptoms, and blood tests in the Sept. 18 Neurology (69:1236–1244).
Study leader Christian G. Bien, MD, of the department of epileptology at the University of Bonn in Germany, explained that patients with TLE-HS typically have recurrent seizures starting in childhood or adolescence. And most of these cases were caused by some precipitating injury.
Adult onset TLE-HS is sometimes the result of a precipitating injury, but more often the etiology is unknown, Dr. Bien said. And, in those cases, there may be reason to suspect limbic encephalitis.
“Clinicians should try to find out the cause of recent onset temporal lobe epilepsies in adults, and MRI is certainly one of the first steps,” Dr. Bien told Neurology Today. “If an otherwise unexplained temporomedial T2 or FLAIR signal increase is found, limbic encephalitis may be tentatively diagnosed.” [See “Criteria for Limbic Encephalitis.”]
DIAGNOSING LIMBIC ENCEPHALITIS
Limbic encephalitis (LE) is characterized by degenerative changes of the hippocampus and amygdaloid nuclei with memory loss, confusion, seizures, and progressive dementia; there is sometimes a tumor elsewhere in the body.
Dr. Bien said a diagnosis of definite limbic encephalitis can be made in adults by demonstrating a limbic syndrome, including the combination of impaired recent memory and temporal lobe seizures, plus evidence of either a tumor or at least one onconeuronal antibody such as anti-Hu or anti-Ma in serum. [See “Antibodies Associated with Paraneoplastic Cerebellar Degeneration (PCD).”]
Alternatively, the diagnosis of limbic encephalitis may be confirmed by finding serum antibodies against voltage-gated potassium channels, which may be found in patients without underlying malignancy, he said.
Dr. Bien said the diagnostic process begins with MRI evidence of temporomedial swelling and T2/FLAIR signal increase. In weeks or months, the hippocampi become atrophic but retain increased signal, evolving into hippocampal sclerosis.
“This means that in an adult with new onset of temporal lobe epilepsy and otherwise unexplained hippocampal pathology on brain MRI, such as hippocampal sclerosis without a clear history of prior precipitating injury, the clinician should be aware that limbic encephalitis could be the actual precipitating injury,” he explained. “The clinician should then search for an underlying malignancy as well as onconeuronal and potassium channel antibodies.”
Immunotherapy with intravenous steroids or immunoglobulins may improve outcome significantly, Dr. Bien said.
Dr. Bien and colleagues performed a retrospective analysis of history, clinical and paraclinical findings, brain MRI, and outcome of surgical treatment including histopathology of all patients with TLE-HS at a tertiary care center within six years of epilepsy onset between 1999 and 2005.
Thirty-eight patients were identified; the median age for seizure onset was 37.8 years. Eleven patients (29 percent) were classified as having secondary hippocampal sclerosis related to an initial precipitating injury such as head trauma or febrile seizures. Seven patients (18 percent) were classified as idiopathic.
However, nine patients (24 percent) had a diagnosis of definite LE, and another 11 (29 percent) showed the typical LE pattern of MRI findings with hippocampal swelling evolving into atrophy with continuous FLAIR/T2 signal increase; they were diagnosed as having possible LE.
Autoantibodies to voltage-gated potassium channels were present in the serum of seven patients with definite LE. In two patients with definite LE, serum autoantibodies to onconeuronal antibodies led to the diagnosis of tumor indicative of a neoplasm. In contrast, none of the eleven patients with hippocampal sclerosis after precipitating brain injury had autoantibodies.
In addition, bilateral hippocampal abnormalities were more frequent in the two LE subgroups (60 percent) — those with probable and definite LE — than in the two non-LE subgroups (22 percent). The significantly higher frequency of bilateral abnormalities in the LE groups suggests that LE mostly causes bilateral hippocampal damage whereas in those with precipitating injury or dual pathology cases, as well as in the idiopathic ones, only one hippocampus is usually affected, the study authors wrote in the Neurology paper.
From a clinical perspective, these results suggest a need for autoantibody testing in any patient with unexplained adult-onset TLE, particularly if MRI changes are bilateral and progressive, the authors wrote. Also, early immunosuppressive treatments might help prevent progression, they said.
Dr. Bien noted that adult-onset temporal lobe epilepsy with hippocampal sclerosis is not common. “If it occurs, a comprehensive assessment of the patient is needed to make a diagnosis of the underlying cause as soon as possible,” he said. “If there is no CNS tumor, there might be limbic encephalitis. This may be the consequence of a treatable peripheral malignant disease that might respond to immunotherapy and improve the long-term outcome of the brain disorder.”
Neurologist Gregory Cascino, MD, hailed the study as a methodologically rigorous exploration of the etiology of adult-onset temporal lobe epilepsy, with important implications for prevention, diagnosis, and treatment.
Dr. Cascino, professor of neurology at Mayo Clinic College of Medicine in Rochester, MN, and chair of the division of epilepsy at the Mayo Clinic, was not involved with the study.
“What these authors have done is take a cohort of temporal lobe epilepsy patients with idiopathic hippocampal sclerosis and shown that they may have antibodies against certain transmitters that might be important in the pathogenesis of seizure disorders,” Dr. Cascino said. “In some of these patients who have these antibodies, they may have an underlying medical condition, such as a cancer, that needs to be diagnosed and treated.
“The authors have provided some very significant preliminary evidence that intractable epilepsy may be caused by an autoimmune process,” he said.
CRITERIA FOR LIMBIC ENCEPHALITIS
The study authors applied the following criteria to characterize definite limbic encephalitis (LE) and probable LE in patients with temporal lobe epilepsy with hippocampal sclerosis:
* Clinical features (temporal lobe seizures; episodic memory impairment)
* Temporomedial MRI abnormalities — initial hippocampal swelling with signal increase, to volume normalization, and atrophy with signal increase
* Serum evidence of onconeuronal antibodies or a neoplasm within five years of onset of neurologic dysfunction
* Serum evidence of antibodies to voltage-gated potassium channels but no tumors present
* Temporomedial MRI abnormalities (as evidenced in criteria for definite LE)