The authors’ observations
Ms. P presented with an interesting manifestation of neuropsychiatric symptoms in the context of FD; however, common cardiac and cerebrovascular features of the disease were not fully developed. Ms. P experienced progressive cognitive and behavioral changes for 2 years before her admission (Table 2), which may represent a prodromal period leading up to what appeared to be a frontally mediated dementia syndrome. Müller et al15 described a patient with FD who displayed a behavioral profile similar to Ms. P’s that included increasingly unstable mood for at least 3 years, borderline personality disorder features, and rapidly fluctuating mood. A case study reported that risperidone, 1 mg/d, used to treat psychosis in a male FD patient caused extrapyramidal symptoms.16
Ms. P presented with no evidence of stroke or transient ischemic attacks, which is atypical for FD patients with cognitive impairment. However, neuroimaging did reveal frontal atrophy that may be associated with her impulse control deficits, risk-taking behavior, emotional instability, and poor judgment. Her cognitive testing was notable for impairment and exaggeration of symptoms consistent with personality disorder symptoms. Possible reasons for exaggeration include a desire to maintain the sick role or secondary gain related to obtaining disability income.
Ms. P’s behavior pattern could be caused by dementia with frontal features, possibly secondary to FD, in combination with personality and psychiatric pathology.
The mainstay of FD treatment is enzyme replacement therapy (ERT), which addresses the underlying enzyme deficiency. Available research indicates that ERT may reduce symptom severity and slow disease progression; however, further studies are needed to determine if it will reduce outcomes such as stroke, ischemic heart disease, or renal disease.2
Table 2
Symptoms that preceded Ms. P’s admission
| Time frame | Symptoms |
|---|---|
| 24 months before admission | Depressed mood Decreased ability to manage independent activities of daily living (eg, finances, cooking) Minimal objective cognitive impairment |
| 12 months before admission | Increased depression Mild to moderate decline in cognitive functioning Visual and auditory hallucinations Impulsivity/poor impulse control Irrational decision-making Increased risky behavior |
| 6 months before admission | Severe cognitive decline with cognitive symptom exaggeration Psychiatric symptom exaggeration Disorganized thinking Continued risky behavior and poor decision-making |
TREATMENT: Persistent deficits
Ms. P is started on risperidone rapidly titrated to 4 mg/d for delusional thinking and behavioral disturbance. After initially improving, she develops delirium when risperidone is increased to 4 mg/d. She has visual hallucinations, marked confusion with disorientation, worsened short-term memory, and an unsteady, shuffling gait. Risperidone is tapered and discontinued and Ms. P’s motor symptoms resolve within 2 days; however, she remains confused and delusional. We start her on quetiapine, 25 mg/d titrated to 50 mg/d, and her agitation and delusional thinking progressively decline. Memantine, titrated to 20 mg/d, and rivastigmine, started at 3 mg/d titrated to 9 mg/d, are added to address her cognitive symptoms.
Over several weeks, Ms. P’s mental status slowly improves and her drug-induced delirium completely resolves. However, she has persistent cognitive impairment characterized by compromised short-term memory and poor insight into her medical and psychological condition. She maintains unrealistic expectations about her ability to live independently and return to the workforce. The treatment team recommends that Ms. P’s daughter pursue guardianship and that she receive around-the-clock supervision after discharge from the hospital.
Table
Ms. P’s neuropsychological assessment results
| June | November | |
|---|---|---|
| Intellectual functioning | ||
| Wechsler Adult Intelligence Scale-III | ||
| FSIQ | 60 | |
| VIQ | 68 | |
| PIQ | 56 | |
| Ravens Colored Progressive Matrices | 70 | |
| Premorbid intellectual functioning estimates | ||
| Peabody Picture Vocabulary Test-2 | 89 | |
| Barona Demographic Estimate | 104 | 104 |
| North American Adult Reading Test | 99 | |
| Memory functioning | ||
| Wechsler Memory Scale-III | ||
| Immediate memory | 45 | |
| General delay memory | 47 | |
| Auditory recognition delay | 55 | |
| California Verbal Learning Test-II | ||
| Trial 1 (immediate recall) | <60 (raw = 3) | |
| Trial 5 | <60 (raw = 3) | |
| Total Words Learned | <60 (raw = 15) | |
| Short Delay Free Recall | <60 (raw = 2) | |
| Long Delay Free Recall | <60 (raw = 4) | |
| Executive functioning | ||
| Trail Making Test A | 88 | 88 |
| Trail Making Test B | failed to understand | failed to understand |
| Wisconsin Card Sort-64 | ||
| Number of categories | <60 (raw = 0) | |
| Errors | 81 | |
| Percent conceptual level responses | 74 | |
| Perseverative responses | 107 | |
| Perseverative errors | 108 | |
| COWAT FAS | 65 | 69 |
| Category exemplar | 69 | 80 |
| Motor functioning | ||
| Finger Tapping Dominant Hand | 68 | |
| Finger Tapping Non-Dominant Hand | 62 | |
| Invalidity/effort | ||
| TOMM | ||
| Trial 1 | raw = 34 | raw = 37 |
| Trial 2 | raw = 42 | raw = 45 |
| Recognition | raw = 44 | |
| MSVT verbal | fail | |
| MSVT nonverbal | fail | |
| Scores provided are standardized (mean = 100; SD = 15). Raw scores are also provided when indicated. COWAT: Controlled oral word association test; FSIQ: Full Scale IQ; MSVT: Medical Symptom Validity Test; PIQ: Performance IQ; TOMM: Test of Memory Malingering; VIQ: Verbal IQ | ||
Related Resources
- National Institute of Neurological Disorders and Stroke. Fabry disease information page. www.ninds.nih.gov/disorders/fabrys/fabrys.htm.
- National Fabry Disease Foundation. www.thenfdf.org.
- Rozenfeld P, Neumann PM. Treatment of Fabry disease: current and emerging strategies. Curr Pharm Biotechnol. 2011;12(6):916-922.
Drug Brand Names
- Donepezil • Aricept
- Memantine • Namenda
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Rivastigmine • Exelon