Mr. A, an Afro-Caribbean man, came to our facility at the age of 22 after carrying the diagnosis of schizophrenia, paranoid type, for 6 months. He had no significant past medical history, apart from the diagnosis of essential hypertension, treated with metoprolol, no history of intellectual deficits or need for educational remediation, and no history of alcohol or drug abuse. There was no known family history of neurological or psychiatric disease, although little history was available from the paternal side.

Mr. A’s symptoms dated from age 21, when he was on active military duty. At that time, he began to complain that the left side of his brain was “swollen” and “had a sore on it” and that the material of his brain moved, preventing thoughts from traveling from one side of the brain to the other and causing his face to twist and his left eye to roll back into his head. These complaints were interpreted as somatic delusions. He developed paranoid ideation concerning his shipmates and ideas of reference regarding the television. Auditory hallucinations were present throughout most of the course of his illness but were never prominent, and details were not documented. Nine months after initial presentation at age 21, he required hospitalization and was diagnosed with schizophrenia, for which he was given risperidone with limited response. After discharge, he was switched to olanzapine. When interviewed at age 27, he was working and enrolled in a technical school but reported that his personality had changed from being “outgoing and full of energy” to “introverted and spending all my time alone.”

Over the next 6 years, Mr. A’s psychotic symptoms were treated sequentially with risperidone, olanzapine, and ziprasidone, titrated to effectiveness but with significant dose variation due to side effects. Even with the best clinical response, the putative somatic delusions remained, as did residual paranoid ideation, ideas of reference, and auditory hallucinations. He complained of “tightness” around the eyes and stiffness in the head, neck, and knees. Usually these complaints were interpreted as a psychotic elaboration of neuroleptic side effects and treated with benztropine but with minimal response.

Mr. A complained of anxiety, particularly in social situations, which exacerbated both his paranoia and somatic delusions. To address anxiety, he was treated with selective serotonin reuptake inhibitors and intermittently with benzodiazepines, which were variably effective.

At age 27, while receiving a trial of ziprasidone, Mr. A started to stutter (most prominently when he was anxious) and developed lip and mouth “twitching”; however, he received a total score of 1 on the Abnormal Involuntary Movement Scale (1), below the threshold for the diagnosis of tardive dyskinesia. He also complained of weakness and depressed mood. He was unable to concentrate and was failing all of his examinations at technical school. Ziprasidone was switched to olanzapine, but he continued to complain of problems with memory (despite scoring 30 of 30 on the Mini-Mental State Examination) and of feeling “clumsy,” “off balance” at times, and “cloudy.” This last symptom caused him to have difficulties at work. Upon subsequent examination, oral dyskinesias were noted, and his speech was described as “slurred.”

At age 29, his anxiety worsened, and he developed panic attacks. His somatic complaints and speech difficulty progressed. An otolaryngological evaluation revealed a hyperfunctioning larynx, with scissoring of the left arytenoid cartilage. The anxiety, stuttering, and comprehensibility improved both subjectively and objectively with paroxetine titrated to 40 mg/day.

Psychotic symptoms, anxiety, and medication side effects intermittently interfered with his ability to study and work; however, he was able to complete his degree from technical school and intermittently work in various technical jobs, at times holding two jobs simultaneously, until the age of 31.

At this time, Mr. A started to complain of dysphagia with solids, “dizziness” with positional change, cramping of his hands, occasional spasms when holding objects, dry mouth, and blurred vision. Upon neurological examination, deep tendon reflexes were diminished throughout, and there was mild distal vibration loss and mild gait ataxia. His eye movements were normal.

At age 32, Mr. A experienced a marked decline in cognitive function. Neuropsychological testing revealed significant impairments in some—but not all—domains. Working memory appeared intact, but there was impairment in consolidation and recall. Timed aspects of executive function testing, verbal fluency, and naming ability were all impaired, but alternation and accuracy in these tasks were good, suggesting psychomotor slowing with less evidence of typical frontal dysfunction. These results indicated subcortical rather than cortical dementia.

Based on clinical assessment and a neurological examination, medication adjustments resulted in some improvement in cognitive function, truncal and gait ataxia, and alertness.

Upon repeat neurological evaluation (5 months after the first), there was moderate, generalized chorea, mild scanning dysarthria, staccato speech, moderate dysmetria, and dysdiadochokinesia, more pronounced on the left. His gait was slightly wide-based, with mild bilateral foot drop. He was unable to perform tandem gait. There was diminished joint position and vibration sense in his toes and fingers bilaterally. Deep tendon reflexes were absent throughout, and plantar responses were bilaterally flexor. His eye movements remained normal.

At the time of the second neurological evaluation, Mr. A underwent extensive laboratory testing. With the exception of an elevated prolactin level of 28.5 ng/ml (reference range=0–15 ng/ml), all laboratory tests were within normal limits, including CBC; peripheral smear; erythrocyte sedimentation rate; serum chemistries; liver enzyme tests; vitamin B₁₂; folate; rapid plasma reagin; HIV; antinuclear antibody; thyroid stimulating hormone; ceruloplasmin; ferritin; 24-hour urine copper excretion; apolipoprotein B, anti-Ri, anti-Hu, and antineuronal nuclear antibodies; Lyme titer; CSF glucose; protein; cell count; and 14-3-3 protein. Genetic testing for Friedreich’s ataxia, Huntington’s disease, SCA1, SCA3, SCA6 was negative.

Magnetic resonance imaging showed minimal bilateral periventricular and subcortical high signal white matter changes consistent with chronic microvascular ischemic changes due to hypertension, as well as moderate bilateral cerebellar atrophy; the pons appeared slightly symmetrically reduced in size.

Electroencephalography was normal during the awake state but showed a large amount of biphasic delta waves during drowsiness, which could be either normal or consistent with mild diffuse cerebral dysfunction. At the time, Mr. A was receiving risperidone, 6 mg/day; paroxetine, 40 mg/day; and benztropine, 1.5 mg/day. Electromyography was normal except for absent H reflexes. A modified barium swallow showed mild spasm of the distal esophagus, and laryngoscopy showed cricopharyngeal spasm and dystonia (spasmodic dysphonia). SCA2 testing showed 22 CAG repeats on one allele and 39 on the other (upper limit of normal=31).