History
Mr. Tsang was a 70-year-old gentleman. He is a chronic smoker and non-drinker. He was a retired dim sum chef.
He was admitted for an episode of fall. He was noted to have an altered mental state upon admission. He was on regular over-the-counter carisoprodol, a muscle relaxant.
His sister reported a history of recurrent falls in the past 6 months.
His daughter suffered from adult-onset bilateral lower limb weakness that rendered her to be chair-bound. She underwent genetic testing and was found to have a homozygous mutation in the ATP13A2 gene. Mr. Tsang was found to be a carrier for the same gene.
Physical examination
Neurological examination was pertinent for a disoriented patient, an upper motor neuron type left-sided facial and limb weakness, and subtle signs of Parkinsonism including reduced blinking, finger bradykinesia, and cautious small-stepped gait.
There were no abnormal sensation or cerebellar signs.
Investigations
A plain CT brain demonstrated a right centrum semiovale lacunar infarct.
A contrast MRI brain confirmed the presence of scattered acute to subacute right cerebral infarcts confined to the anterior circulation.
An electroencephalogram revealed mild asymmetrical right-sided slowing.
Cerebrospinal fluids were not suggestive of meningeal inflammation.
Thought process
The pathology was likely localized to the cerebral level.
Given the acute onset altered mental state with left sided focal neurological signs, a right cerebral acute ischemic stroke was the most probable etiology. Toxic causes, provided the carisoprodol use, may be a less likely contributory component.
In view of the history of subacute recurrent falls, carrier state of the ATP13A2 mutation, and the family history of a suspected genetic neurodegenerative disease, consideration was given to the possibility of a neurogenetic disease smouldering in the background.
ATP13A2 mutation has been reported to be associated with a wide phenotypic spectrum, including early onset parkinsonism (Kufor-Rakeb syndrome), hereditary spastic paraplegia (SPG 78), neuronal ceroid lipofuscinosis type 12, and amyotrophic lateral sclerosis; with additional features such as cerebellar ataxia, cognitive impairment, seizures.
Bearing in mind the autosomal recessive nature of these disorders, clinical manifestation in this patient, a presumed simple heterozymous mutation carrier, would be atypical.
Moreover, the patient currently does not display overt clinical signs suggestive of these disease syndromes apart from the subtle hints of Parkinsonism, although physical findings may be overshadowed by the acute stroke features and cognitive impairment.
Next steps
Standard treatment for an acute ischemic stroke was recommended. Right anterior circulation large vessel work up was suggested for the infarct topography compatible with an artery-to-artery embolic shower.
Further characterization of the daughter’s phenotype, such as age of onset, tempo of disease progression, and extra-spinal manifestation, was required to allow for correlation with her genotype and substantiation of the mutation’s pathogenicity. This could carry prognostic value for the patient’s carrier status.
Longitudinal clinical monitoring of Mr. Tsang’s neurological symptoms and signs will be necessary for the suspected genetic predisposition, particularly after a period of recovery following the acute ischemic stroke.