Prodromal headache in anti-NMDAR encephalitis: An epiphenomenon of NMDAR autoimmunity.

OBJECTIVE: To investigate the nature of prodromal headache in anti-NMDA receptor (NMDAR) encephalitis. METHODS: Retrospective review of the clinical information of 39 patients with anti-NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12-47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report. RESULTS: Twenty-two patients (65%) reported headache either transiently (n = 5) or continuously (n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1-29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/µl [range, 6-311/µl] vs. 30/µl [range, 2-69/µl], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them. CONCLUSIONS: Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody-mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking "dissociative anesthesia," we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.

[Headache immunology]. / Immunologiia golovnoi boli.

The overview is dedicated to the neuroimmunological mechanisms of headache development and chronification. Based on the analyzed data, the authors determined the relationship between immunological parameters and duration, intensity and other characteristics of this disease. These findings confirm that immunocompetent cells can be used as headache biomarkers and predictors of treatment efficacy. Questions about the role of separate parts of the immune system in the development and maintenance of a headache require further research. Studies of humoral immunity appeared to be very promising.

Headaches related to rheumatologic disease.

Headaches are a common, but under-recognized and understudied symptom in the context of the rheumatic diseases. They can result from intracranial pathology, such as parenchymal and meningeal inflammation, thrombosis, space-occupying lesions, and more. Inflammation, irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses can equally cause headaches. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, and generally require only symptomatic relief, the former type of headaches may signal disease manifestation, progression, or complication. Thus, familiarity with common and uncommon headache syndromes related to rheumatologic disorders as well as with their possible underlying disease processes and mechanisms is important. This will help to successfully develop an effective approach toward the evaluation of patients presenting with headaches in a rheumatologic context, and, ultimately, diagnose and treat potentially severe underlying disease.

Flow cytometric assessment of anti-neuronal antibodies in central nervous system involvement of systemic lupus erythematosus and other autoimmune diseases.

The objective of this study is to evaluate the association between anti-neuronal antibody (anti-NA) and central nervous system (CNS) manifestations of systemic lupus erythematosus (SLE) and other rheumatic diseases using a flow cytometric method. Anti-NA was measured by flow cytometry in serum and cerebrospinal fluid (CSF) samples from patients with SLE (n=44 for serum, n=17 for CSF), other rheumatic diseases (n=64 for serum, n=21 for CSF) and from healthy controls (n=65 for serum, n=18 for CSF). Serum anti-NA was more frequently observed in SLE (31.8%, 14/44) than in other rheumatic diseases (4.7%, 3/64, P<0.001) or in healthy controls (0%, 0/65, P<0.00001). In SLE patients, the frequency of serum anti-NA was significantly higher in CNS-SLE (76.5%, 13/17) than in non CNS-SLE (3.7%, 1/27, P<0.000001). CSF anti-NA was detected in 88.2% (15/17) of CNS-SLE and was more frequently detected in CNS-SLE (15/17, 88.2%) than in other rheumatic diseases with CNS involvement (1/21, 4.8%, P<0.000001) or in healthy controls (0/18, P<0.000001). In conclusion, serum anti-NA was more frequently found in CNS-SLE than in non CNS-SLE, other rheumatic diseases or in healthy controls. The frequency of CSF anti-NA in CNS-SLE was significantly higher than in other rheumatic diseases with CNS involvement or in healthy controls.

Inflammatory mechanisms in cervicogenic headache: an integrative view.

Cervicogenic headache is a relatively common and still controversial form of headache that originates from the neck structures. The pathophysiology probably results from various local pain-producing factors, such as intervertebral dysfunction, but the frequent coexistence of a history of head traumas still plays an important role. This report represents a series of pathophysiologic studies performed for patients with cervicogenic headache and the results achieved by a new pharmacologic treatment for the disease.

The clinical characteristics of new daily persistent headache.

New daily persistent headache (NDPH) is a subtype of chronic daily headache. The literature on NDPH is scant and its true aetiology is unknown. A retrospective chart review was carried out from a computerized database at the Jefferson Headache Centre from August 1997 to May 2000 to identify patients with NDPH using the Silberstein et al. criteria. Forty women and 16 men were identified. Age of onset ranged from 12 to 78 years. The peak age of onset was the second and third decade in women and the fifth decade in men. Eighty-two per cent of patients were able to pinpoint the exact day their headache started. Onset occurred in relation to an infection or flu-like illness in 30%. A prior headache history was found in 38% of patients. A family history of headache was documented in 29%. The duration of daily headache ranged from 1.5 h to 24 h; 79% were continuous. Nausea occurred in 68% of patients, photophobia in 66%, phonophobia in 61%, and lightheadedness in 55%. Laboratory testing and neuroimaging in all patients was normal except for Epstein-Barr virus antibody titres, which were positive in 71% of seven patients tested, representing past infection. NDPH appears to be a female-predominant disorder, marked by a continuous daily headache with associated migrainous symptoms. Over 80% of patients could state the exact date their headache began. One-third of patients developed NDPH with a flu-like illness.

Proinflammatory cytokines in cervicogenic headache.

Interleukin-1 beta (IL-1 beta) and Tumour Necrosis Factor-alpha (TNF-alpha) exert their multifunctional biological effect by promoting and increasing the molecular events of cellular inflammation. The aim of this study was to find out whether the cytokine pattern of cervicogenic headache (CH) patients tends, like that seen in cluster headache, towards an inflammatory status. Fifteen CH patients, diagnosed according to the 1998 CHISG criteria, were analysed for serum IL-beta (ELISA) and TNF-alpha (bioassay and ELISA) both during the natural course of a painful attack and during a phase of mechanically worsened pain. The control groups consisted of 15 migraine without aura (MWA) patients and 15 historically healthy subjects. The MWA patients were studied both during (MWA-IN) and outside (MWA-OUT) a migraine attack. Higher levels of both IL-1 beta and TNF-alpha were detected in the sera of CH patients than in that of MWA-IN and MWA-OUT and C subjects. A difference also emerged in CH between spontaneous and mechanically worsened pain phases. We conclude that the degree of cytokine production may depend on the different pathophysiological mechanisms at work in MWA and CH.