Key Takeaways
A 43-year-old woman presented with insidious onset of neurocognitive decline, alien limb phenomenon, and personality changes.
A case report by Anza Zahid, MD, a neurology resident at the Stanley H. Appel Department of Neurology at Houston Methodist Hospital, Houston, and colleagues documented a significantly underdiagnosed and frequently misdiagnosed disease.
The Patient and His History
A right-handed woman presented with left extremity loss of function and personality change for over 1 year at the neurology outpatient clinic. After the birth of her fourth child, she began experiencing frequent headaches. She also became withdrawn, forgetful, and volatile in her mood, crying often and laughing inappropriately. She had no family history of neuropsychiatric or memory disorders.
On the Montreal Cognitive Assessment, she scored 13 out of 30, losing points in visual-spatial testing, delayed memory, and calculation. Neurologic examination revealed oculomotor apraxia and three beats of nystagmus on horizontal right-sided gaze. The grasp reflex was present bilaterally. She demonstrated significant incoordination of her left hand, stating her left hand has a mind of its own. She had increased tone in all her extremities, with an admixture of rigidity and spasticity on the left side, but her motor strength was normal. Deep tendon reflexes were exaggerated bilaterally. Sensory testing was normal. On gait assessment, she walked unassisted, dragging her left foot in a plantar flexed position.
Findings and Diagnosis
Head CT showed ventriculomegaly and punctate calcification in the frontal lobe. Brain MRI revealed diffusion restriction and T2 periventricular hyperintensity with atrophy of the genu and anterior body of the corpus callosum. Cerebrospinal fluid analysis showed 2 white blood cells/mm3, 435 red blood cells/mm3, 48 mg/dL protein, 62 mg/dL glucose (serum glucose, 80 mg/dL), a normal immunoglobulin G index, and a synthetic rate.
Based on the patients’ history of headaches, left-sided weakness, and cognitive and personality changes, the differential diagnoses included cerebral venous sinus thrombosis, vascular aetiology (stroke, cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, and Susac disease), and neurodegenerative conditions such as behavioural variant frontotemporal dementia, corticobasal degeneration, post-COVID demyelination syndrome, or multiple sclerosis.
A frontal brain biopsy revealed extensive myelin loss with macrophage infiltration and the presence of neuroaxonal spheroids. Genetic testing confirmed the diagnosis of heterozygous CSF1R c.1765G > A (p.Gly589Arg) gene mutation. No pathogenic variants of NOTCH3 were detected. Therefore, the diagnosis of CSF1R-related disorder was confirmed.
The patient was administered high-dose steroids without significant improvement. An induction dose of intravenous immunoglobulin (2 g/kg) showed a transient benefit per oral report. For left upper extremity spasticity, she was offered botulinum toxin injections.
Discussion
“The patient’s disease had progressed too far, rendering her ineligible for clinical trials. The patient was administered high-dose steroids without significant improvement. An induction dose of intravenous immunoglobulin (2 g/kg) showed a transient benefit per oral report. For left upper extremity spasticity, she was offered botulinum toxin injections. The family was referred to a genetic clinic for counselling for her four children,” wrote the authors.
This article was translated from Univadis Germany.