Men with N-methyl-D-aspartate (NMDA) receptor antibodies (NMDAr-Abs) encephalitis present different from women, according to a recent study (Viaccoz A, et al. Neurology. 2014;82:556-563). Adult men are more likely to present with seizures, whereas women rarely present with seizures and are much more likely to present with behavioral and psychiatric features as their first symptom. Males and females have a similar course of global progression and similar recovery.
“Our take-home message is that the first symptoms of NMDAr-Abs encephalitis in adult males are different than in females. As in children with this disease, the first symptoms in adult males are frequently partial seizures rather than abnormal behavior and psychiatric presentations,” explained senior investigator Jérôme Honnorat, MD, PhD, Professor, Service de Neuro-Oncologie, Hôpital Neurologique, Bron, France, in an interview with the Valued-Based Care in Neurology. “This is important for neurologists to know, because they must be aware that adult male patients with partial seizure, normal MRI [magnetic resonance imaging], and inflammation of the cerebral spinal fluid may have an NMDAr-Abs encephalitis.”
Although relatively rare, NMDAr-Abs encephalitis could represent between 2% and 40% of the cases of suspected viral encephalitis, Dr Honnorat said.
Viaccoz and colleagues pointed out that most reports of this disease (which was first described in (Dalmau J, et al. Ann Neurol. 2007;61:25-36) include both females and males. However, unlike in females, the clinical course of the disease has been less clear in male patients.
The present study included 13 adult male patients diagnosed with NMDAr-Abs encephalitis using 2 different tests to confirm the results and to avoid false-positives. According to the presenting symptoms, males can be categorized as seizure, psychiatric and behavioral disorders, or cognitive dysfunction. Seizures were the first presenting signs in 8 of the 13 patients in the study; 4 of them had partial seizures, and within 12 days, partial seizures were followed by psychiatric symptoms (ie, hallucinations, psychosis, agitation with hypersexuality, psychosis, and fluctuating levels of consciousness) or cognitive symptoms (ie, confusion associated with speech disturbances).
Of the male patients who did not present initially with seizures, 23% had cognitive dysfunction and 7.7% had psychiatric symptoms.
Of the 13 adult males, 12 received immunotherapy with corticosteroids and/or intravenous immunoglobulin; 8 patients received second immunomodulatory treatment with rituximab or cyclophosphamide. Severe disease occurred in 9 patients, and 9 patients were admitted to the hospital. Favorable outcomes were reported in 10 patients, and 6 patients achieved complete recovery. Relapse occurred in 3 patients.
Dr Honnorat stated that early recognition of the disease is important, because “we suppose that early immunomodulatory treatment could improve the rate of total recovery and could accelerate healing.”
The investigators compared the 13 male patients with 58 female patients identified in their database. Tumors were present in 24 (23 ovarian teratomas and 1 breast cancer) females versus only 1 (schwannoma) tumor in adult males.
The first symptoms in males differed from females: 67% of females had behavioral and psychiatric symptoms at initial presentation versus 7.7% of the males (P >.01). Seizure at onset was observed in 8 (13.8%) of the 58 female patients and in 8 (61.5%) of 13 male patients (P <.001).
Subsequent neurologic symptoms are observed earlier in female patients than in males with seizure at disease onset (median of 2 days for females vs 13 days for males; P <.01). However, all symptoms were equally present in both sexes at different time points.
In an accompanying editorial in the same issue of Neurology, Titulaer and Dalmau wrote that the study provided the novel observation that adult males present with seizures more often than females (who usually initially present with abnormal behavior and psychiatric symptoms).
In a previous series of 577 patients, Titulaer and Dalmau confirmed that seizures were more often the initial symptom in adult males (27% vs 11% of females), but they also found that psychiatric symptoms remained the most common initial symptoms (54% of men vs 67% of women).
They suggest that women with acute psychiatric symptoms are more often suspected to have this disorder than men with a similar presentation. “In men antibody testing and other ancillary investigations may not be considered until they develop seizures.”
It is possible that regardless of the presenting symptoms, in men the diagnosis is delayed rather than missed. “The astute observation of Viaccoz et al should help improve diagnosis in adult men, prompting early therapy and possibly better outcomes,” they noted.