BACKGROUND: Leukoencephalopathy with neuroaxonal spheroids is a rare cause of severe, subacute dementia that usually presents in childhood and is inherited in an autosomal dominant pattern. The authors present clinical, radiologic, and pathologic features of adult-onset, sporadic cases mimicking cerebral-type progressive MS. METHODS: Five patients referred to an MS subspecialty clinic from 1999 to 2006 suspected of having primary cerebral MS. All patients were reviewed clinically, radiologically, and pathologically at Mayo Clinic Rochester. Diagnostic brain biopsies were examined by two neuropathologists. RESULTS: All patients had severe, progressive cognitive and motor impairment, often with prominently asymmetrical features and diffuse nonenhancing subcortical white matter lesions on brain MRI. Cerebrovascular and spinal cord imaging were normal. CSF showed elevated neuron-specific enolase without elevated oligoclonal bands or IgG index. Extensive evaluations for alternative diagnoses were unrevealing. Pathologic examination confirmed leukodystrophy with neuroaxonal spheroids and pigmented glia on all patients. Therapies initiated did not alter the severe progressive disease course. CONCLUSIONS: Leukoencephalopathy with neuroaxonal spheroids occurs sporadically, in adults, and mimics cerebral-type MS or other leukodystrophies. Brain biopsy may be diagnostic in life; however, no treatment is known to be effective. Pathologic diagnosis is important to avoid potentially toxic therapies aimed at CNS inflammatory diseases such as MS.
BACKGROUND:Leukoencephalopathy with neuroaxonal spheroids is a rare cause of severe, subacute dementia that usually presents in childhood and is inherited in an autosomal dominant pattern. The authors present clinical, radiologic, and pathologic features of adult-onset, sporadic cases mimicking cerebral-type progressive MS. METHODS: Five patients referred to an MS subspecialty clinic from 1999 to 2006 suspected of having primary cerebral MS. All patients were reviewed clinically, radiologically, and pathologically at Mayo Clinic Rochester. Diagnostic brain biopsies were examined by two neuropathologists. RESULTS: All patients had severe, progressive cognitive and motor impairment, often with prominently asymmetrical features and diffuse nonenhancing subcortical white matter lesions on brain MRI. Cerebrovascular and spinal cord imaging were normal. CSF showed elevated neuron-specific enolase without elevated oligoclonal bands or IgG index. Extensive evaluations for alternative diagnoses were unrevealing. Pathologic examination confirmed leukodystrophy with neuroaxonal spheroids and pigmented glia on all patients. Therapies initiated did not alter the severe progressive disease course. CONCLUSIONS:Leukoencephalopathy with neuroaxonal spheroids occurs sporadically, in adults, and mimics cerebral-type MS or other leukodystrophies. Brain biopsy may be diagnostic in life; however, no treatment is known to be effective. Pathologic diagnosis is important to avoid potentially toxic therapies aimed at CNS inflammatory diseases such as MS.
Authors: Christina Sundal; Jay A Van Gerpen; Alexandra M Nicholson; Christian Wider; Elizabeth A Shuster; Jan Aasly; Salvatore Spina; Bernardino Ghetti; Sigrun Roeber; James Garbern; Anne Borjesson-Hanson; Alex Tselis; Russell H Swerdlow; Bradley B Miller; Shinsuke Fujioka; Michael G Heckman; Ryan J Uitti; Keith A Josephs; Matt Baker; Oluf Andersen; Rosa Rademakers; Dennis W Dickson; Daniel Broderick; Zbigniew K Wszolek Journal: Neurology Date: 2012-07-25 Impact factor: 9.910