Fahr's disease and psychiatric syndromes: A case series.

Fahr's disease is characterized by basal ganglia calcification with clinical manifestations in the form of neuropsychiatric disorders, neurological symptoms, and cognitive symptoms. In this case series, we describe two cases of basal ganglia calcification, one of whom presented with psychotic symptoms and the other with mood symptoms, and discuss the literature with regard to psychiatric manifestations of basal ganglia calcification.

Basal ganglia calcification (BGC) as a neuropathological finding has been described since mid of 1850s.[12] Over the years, it has been extensively studied and is now understood as a neuropathological finding, which can be idiopathic or secondary to genetic, metabolic, and endocrinological disorders. Idiopathic BGC is known as Fahr's disease (FD) and BGC secondary to endocrinological causes is known as Fahr's syndrome. In routine computerized tomography of brain, it has been reported at a frequency of 0.3 to 1.2%.[3] Over the years, studies suggest that BGC is associated with various neuropsychiatric symptoms.[4]

We present two cases of BGC and discuss various neuropsychiatric manifestations seen in patients with BGC.

CASE REPORTS

Case 1

Mrs. A, a 70-year-old female who was premorbidly well adjusted and had no past history of mental disorders presented with an insidious onset illness of 6 months’ duration, characterized by muttering to self, irritability, delusions of reference and persecution, and auditory hallucinations of discussing type. Over a period of 3 months, her psychotic symptoms worsened, and, after this, in addition to the psychiatric symptoms she developed bilateral tremors of hand. On physical examination at first evaluation, she was found to have chewing movements of mouth and bilateral tremors of hand (both resting and intentional). There was no evidence of rigidity and cerebellar signs. Her investigations in the form of hemogram, blood biochemistry including serum calcium levels, liver function tests, renal function tests, thyroid function tests, parathyroid hormone levels, electroencephalogram, and electrocardiogram did not reveal any abnormality. However, her fasting and post-prandial glucose levels suggested that she was suffering from diabetes mellitus. In view of the late age of onset of psychosis, a non-contrast computerized tomography (NCCT) of brain was done, which showed calcification of bilateral globus pallidus. In view of the same, in liaison with a neurologist, a magnetic resonance imaging of brain was done, which showed nonspecific T2 flair hyperintensities in bilateral centrum semiovale and periventricular white matter. In view of the BGC, history was further explored, which did not reveal any family history of psychosis or BGC. In view of the late-onset psychosis, presence of movement disorder, BGC on NCCT, lack of evidence of parathyroid abnormality, and lack of family history of BGC or psychosis, a diagnosis of Fahr's disease (FD) was considered. She was managed with T. Olanzapine 7.5 mg/day with which she showed improvement over a period of 12 weeks. Her diabetes mellitus was managed with Glimeside 1 mg/day.

Case 2

Mr. X, 65-year-old male who was premorbidly well adjusted and had past history of pulmonary tuberculosis (at the age of 42 years) and blindness of left eye (since the age of 45 years) with no family history of mental disorders, presented with an episodic illness which started at the age of 48 years. The first episode was characterized by depressive features in the form of sadness of mood, crying spells, anhedonia, depressive cognitions, increased sleep, and decreased appetite. For this, he was initially treated with T sertraline with which he showed complete improvement. After a few months of remission, he had symptoms of mania in the form of irritability, increased self esteem, grandiosity, overactivity, overfamiliarity, decreased sleep, and increased appetite. He was managed with antipsychotics with which he improved completely.

Over the years, he had 4 episodes of mania, each lasting for 2–4 months, associated with marked dysfunction, and would require treatment for the same. Now, he was symptomatic for about 9 months. He initially had symptoms suggestive of moderate depressive episode without somatic symptoms (as per ICD-10) lasting for 8.5 months, followed by manic symptoms (current episode mania with psychotic symptoms) for 2 weeks with marked socio-occupational dysfunction. Initially, diagnosis of bipolar affective disorder, current episode mania with psychotic symptoms, was considered. However, in view of late age of onset (48 years at the time of first episode), he was evaluated for organic causes.

His investigations in the form of hemogram, blood biochemistry including serum calcium levels, liver function tests, renal function tests, thyroid function tests, electroencephalogram, and electrocardiogram did not reveal any abnormality. A NCCT of brain showed calcification of basal ganglia in the region of globus pallidus. In view of the BGC, parathyroid hormone estimation was done, which did not reveal any abnormality. Magnetic resonance imaging of brain showed mild cerebral atrophy. In view of the late-onset bipolar affective disorder and BGC in the absence of parathyroid abnormality, a diagnosis of FD was considered. He was managed with T. Olanzapine 10–15 mg/day along with T. Clonazepam up to 2 mg/day with which he achieved remission.

DISCUSSION

FD is characterized by BGC with clinical manifestations in the form of neuropsychiatric disorders, neurological symptoms, and cognitive symptoms.[45] Although calcifications can involve other structures, globus pallidus is most commonly involved.[6]

About half of patients with BGC have neurological features in the form of headache, vertigo, movement disorders, paresis, stroke-like events (including episodes resembling transient ischemic attacks), seizures, and syncope. The movement disorders are the most common neurological sign and symptoms and usually manifest as spasticity, gait disorder, speech impairment, Parkinsonism, chorea, tremor, dystonia, and myoclonus.[7] In a review of 213 cases, the authors reported that 22% patients have seizures and 56% of patients have extrapyramidal movement disorders.[8]

With regard to psychiatric manifestations, nearly 40% of patients with BGC present initially with psychiatric features, of which cognitive, psychotic, and mood disorders are common. Some cases may present with anxiety features.[8] Further, studies suggest that the psychiatric symptomatology may change over time. In a review of literature, authors reported mood disorders, both depression and mania (depression much more common than mania) to be the most common psychiatric disorder associated with BGC.[7] It is suggested that mood disorders are initially seen in one-fifth of patients but these eventually occur in about two-third of cases.[89]

Psychosis associated with BGC usually presents with paranoid and psychotic features between the ages of 20 and 40 in FD.[10] The psychotic symptoms may include auditory hallucinations (sometimes musical), complex visual hallucinations, perceptual distortions, paranoid delusions or nondelusional trends, ideas of reference or influence, and catatonia.[7] Some studies suggest that there may be 2 patterns of psychotic presentation in FD, i.e., early onset (mean age about 30 years) with minimal movement disorder and late onset (mean age about 50 years) associated with dementia and movement disorder.[71011]

Cognitive symptoms in FD usually include progressive subcortical dementia in the sixth decade of life.[7] Some authors suggest that dementia may have picture suggestive of fronto-temporal lobe involvement. Among the anxiety disorders, obsessive compulsive disorder is seen in about one-third of patients with BGC. Other less commonly seen disorders in presence of BGC include substance abuse and personality change.[7]

In terms of relationship between calcification and psychiatric manifestations, it has been seen that more extensive calcification and subarachnoid space dilatation correlate with the presence of psychiatric manifestations, but distribution of calcification does not correlate with psychiatric manifestations. In terms of treatment, there is no specific treatment for FD and the course is progressive. However, while using antipsychotics, it is important to remember that patients with FD are more susceptible to neuroleptic malignant syndrome when treated with antipsychotic drugs.[7]

Our first case had features of late-onset psychosis along with movement disorder and BGC. The second case had bipolar disorder, which started at the late age and was associated with BGC. Our cases suggest that whenever patients present with psychiatric manifestations at an atypical age, they must be evaluated thoroughly.