Discussion and conclusions
We report an adult patient with levodopa-responsive parkinsonism and known pathogenic GFAP variant. This patient did not have typical symptoms suggestive of Alexander disease. The adult-onset Alexander disease has various clinical features, mainly speech abnormalities, swallowing difficulties, frequent vomiting, lower limb spasticity and ataxia [3]. It can be found incidentally at autopsy or molecularly confirmed cases without a prior history and it is possible that the patient may never develop symptoms related to this genetic diagnosis [4]. It may be reasonable to infer that abnormalities of the brain MRI are mild, and it is difficult for them to develop symptoms, or they may develop for a lengthy time, and become chronic adaptation or compensation. In contrast, the patient showed not only typical parkinsonism, but also good levodopa responsiveness, indicating a clinical diagnosis of PD. Moreover, this was highly supported by FP-CIT PET findings of presynaptic dopaminergic depletion. To the best of our knowledge, a case of Alexander disease, with both typical parkinsonism and striatal dopamine depletion, has not been reported.
The GFAP variant, when expressed in older ages, causes neuronal loss in the brain especially in the brain stem [5]. In some reports, neuronal loss in basal ganglia are found in adult-onset GFAP variant [6–8], that presence of striatonigral neuronal loss on FP-CIT PET with GFAP variant was first described in this case. An unusual pattern of dopamine depletion with a rostrocaudal gradient in the putamen and caudate nucleus were seen, unlike in patients with PD which shows preferential depletion in posterior putamen with relative sparing of caudate nucleus [9]. The atypical dopamine depletion pattern has not been described or investigated in other Alexander disease patients in the literature and that it could also relate to the interaction of co-pathology.
We present an unusual case wherein clinical PD, and genetic Alexander disease coexist. If MRI findings suggestive of leukoencephalopathy-related disorders are observed in patients with PD, clinicians need to further investigate the possibility of genetic variant of adult-onset leukoencephalopathy, including Alexander disease.