Ill-defined neurological syndromes with autoimmune background: a diagnostic challenge

To define the diagnostic features of a cohort of patients presenting with autoimmune manifestations and atypical neurological features not fulfilling criteria for a well defined neurological or connective tissue disorder.

Twenty-nine such patients were referred to our institution for evaluation. Nine were excluded from this study since they were diagnosed with antiphospholipid syndrome. The remaining 20 patients underwent complete clinical and laboratory evaluation, spinal fluid analysis, minor salivary gland biopsy (if sicca features were present), and were tested for evoked potentials. Magnetic resonance imaging (MRI) scans of the brain were performed in all patients and of the spine in 7.

Brain and/or spinal cord MRI abnormalities were found in all 20 patients. Based on morphologic criteria and distribution, these lesions were classified into 3 subsets: (1) multiple sclerosis (MS)-like (4 patients); (2) vasculitic (8 patients); and (3) nonspecific (8 patients). The most frequent underlying abnormality in patients with subgroups 1 and 2 were the presence of homozygous methylenetetrahydrofolate reductase (MTHFR) mutations (5 of 12, 41.6%). The most common findings among subgroup 3 were the presence of antithyroid antibodies (6 of 8 patients, 75%).

Homozygous MTHFR mutations are frequently encountered in patients presenting with neurological features and MS-like or vasculitic type MRI abnormalities in a setting of autoimmune disease. Nonspecific MRI changes are frequently associated with antibodies against thyroid antigens.