Fahr's disease: A rare neurological disease

Case Report

Fahr's disease: A rare neurological disease

Dinesh Chaudhari a,*, Pushpendra Nath Renjen b

a Internal Medicine Resident, Institute of Neurosciences/Internal Medicine, Indraprastha Apollo Hospitals,New Delhi 110076, IndiabSr. Consultant Neurologist & Academic Coordinator, Institute of Neurosciences, Indraprastha Apollo Hospitals,New Delhi 110076, India

1. Case report

A 40-year-old unmarried female presented to our tertiary carehospital with abnormal involuntary movements involvingboth upper limbs for last 5 years, but no suchmovements werenoticed in the lower limbs. Thesemovements were suggestiveof choreo-athetoid movements. The family also noticed thatfor the same period, the patient had features, such as bouts ofdisorientation, anxiety, personality changes, reckless behav-iour and inappropriate laughter. For these symptoms, she wasunder the care of a psychiatrist, and was put under somemedication. Despite this, she was having a progressive declinein the neurological status.

There was no significant family history of mental illness,dementia or any other physical illness. She did not have any

features of depression. On neurological examination, thepatient was alert, oriented to time, place and person. She hadbursts of laughter. Cranial nerves were normal, as well aspower and sensations were found to be normal. Her speechwas dysarthric and mild choreic involving both upper limbs.She had a score of 20/30 on theminimental state examination.No parietal lobe signs, Parkinson's features or any otherfeatures suggestive of long tract signs.

In order to exclude other differentials that may lead tosecondary intracranial calcification, the patient went througha series of blood tests that included completed blood picture,erythrocyte sedimentary rate, serum iron studies, serumcalcium and phosphate level, serum parathyroid hormonelevel, thyroid hormone level, serum creatinine, serum cerulo-plasmin and urinary copper, serum lactate and pyruvic acid,serological tests for syphilis, HIV and CSF study to rule out

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a r t i c l e i n f o

Article history:

Received 2 April 2015

Accepted 1 May 2015

Available online 12 June 2015

Keywords:

Fahr's syndrome

Dentate nucleus calcification

Bilateral basal ganglia calcification

Movement disorder

a b s t r a c t

A 40-year-old unmarried female presented with abnormal involuntary choreo-athetoid

movements involving both upper limbs for 5 years along with features, such as bouts of

disorientation, anxiety, personality changes, reckless behaviour, inappropriate laughter and

progressive decline in the neurological status. On neurological examination, her speechwas

dysarthric with mild choreiform movements involving both upper limbs. She had MMSE

score of 20/30. MRI scans of the brain plain T1- and T2-weighted axial and flair coronal

images were obtained. It showed calcifications as hyper-intense lesions on T1W and hypo-

intense T2W lesions in bilateral basal ganglion and bilateral dentate nuclei of cerebellum,

that is consistent with Fahr's syndrome.

# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights

reserved.

* Corresponding author. Mobile: +91 8585940681.E-mail address: meet2dinum@gmail.com (D. Chaudhari).

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http://dx.doi.org/10.1016/j.apme.2015.05.0090976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.

other metabolic, infectious causes. All these tests wereessentially normal in our patient. Her electroencephalogramwas also done, which was normal. MRI of the brain plain T1 &T2 weighted axial and flair coronal images were obtained. Itshowed calcifications as hyper-intense lesions on T1W andhypo-intense T2W lesions in bilateral basal ganglion andbilateral dentate nuclei of cerebellum that is consistent withFahr's syndrome (Fig. 1).

2. Discussion

Basal ganglia calcification is also known as Fahr's disease orFahr's syndrome. It is a rare inherited or sporadic neurologicaldisorderwith aworldwide prevalence of<1/1,000,000.1–3 It wasfirst described by German neurologist Karl Theodor Fahr in1930.4 It is characterized by abnormal deposition of calcium inareas of the brain that control movements including basalganglia, thalamus, dentate nucleus, cerebral cortex, cerebel-lum, subcortical white matter and hippocampus.5 Most casespresentwith extra pyramidal symptoms initially. Additionally,they may present with cerebellar dysfunction, speech difficul-ty, dementia and neuropsychiatric symptoms.6 Fahr's syn-drome typically manifests in third or fourth decade of life.

Fahr's disease is most commonly transmitted as anautosomal dominant trait, but it may also be passed on asan autosomal recessive trait, or it may occur sporadically.1,7 Alocus at 14q (IBGC1) has been suggested to be involvedcommonly. At the molecular level, calcification generallydevelops within the vessel wall and in the perivascular space,ultimately extending to the neuron. Due to defective irontransport and free radical production, tissue damage occurswhich leads to the initiation of calcification. It occurssecondarily around a Nidus composed of mucopolysaccharideand related substances. Progressive basal ganglia mineraliza-tion tends to compress the vessel lumen, thus initiating a cycleof impaired blood flow, neural tissue injury and mineraldeposition.8 Endocrine disorders, particularly parathyroiddisturbances are most commonly associated with Fahr'ssyndrome. Many neurodegenerative, inherited and infectiousconditions have also been linked to etiological manifestationsof Fahr's syndrome (Table 1).8

Presentation of disease could vary with the age and courseof illness (Table 2). The clinical features usually includepsychosis, cognition impairment, and symptoms of mooddisorders, epileptic seizures and dementia.9,10 Excessiveextensive intracranial calcification is also associated withpsychiatric manifestation.10

Cummings et al. (1983) have described two psychiatricsymptoms in basal ganglion mineralization, as cases withpsychiatric symptoms appearing in the early period (mean 31years) and in late period (mean 49 years). Motor and cognitivesymptoms in cases with basal ganglion mineralization, whichappears in the late period, are more significant.11

Pallidal lesions may cause disorders related to motivation,judgement and insight in humans. Idiopathic basal gangliacalcification may lead to various neuropsychiatric symptoms.Patients with basal ganglia calcification present initially withpsychiatric symptoms. When psychosis occurs in Fahr'sdisease, it usually presents in persons 20–40 years of age as

a part of the so-called early adult-onset Fahr's disease. Classicschizophrenia-like symptoms have been described, includingauditory hallucinations, paranoid delusions, delusions ofreference and catatonia. Psychotic symptoms that are nottypically associated with schizophrenia have also beendescribed, including musical auditory hallucinations andcomplex visual hallucinations.12

The pathophysiology of psychosis in Fahr's diseaseremains unknown, though previous studies have found a

Table 1 – Etiological manifestations of Fahr's syndrome.

S. no. Etiologies

1 Endocrine disorders Idiopathic hypoparathyroidismSecondary hypoparathyroidismPseudohypoparathyroidismPseudo-pseudohypoparathyroidismHyperparathyroidism

2 Adult onsetneurodegenerativeconditions

Neurodegeneration with brainiron accumulation diseaseNeuroferritinopathyPolycystic lipomembranousOsteodysplasia with sclerosingLeukoencephalopathy

3 Infectious disease Intrauterine and perinatalinfectionCockayne syndrome Type 1Cockayne syndrome Type 2

4 Inherited or earlyonset syndrome

Aicardi-Goutieres syndromeTuberous sclerosis complexBrucellosisCoat's disease

Table 2 – Clinical features of Fahr's syndrome.

S. no. Clinical features

1 Neurological Loss of consciousnessTetanySeizuresEpileptic disorderGait disorderSpasticitySpeech impairmentDementiaMyoclonusComaParoxysmal choreoathetosisDystonic choreoathetosisPapilledema of intracranialhypertensionPleocytosis of CSF

2 Movement disorder ClumsinessFatigabilityUnsteady gaitInvoluntary movements andmuscle cramping

3 Neuropsychiatricfeatures

PsychosisDepressionApoplexiaDeterioration of intelligenceInability to make decisions

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decreased cerebral blood flow matching the distribution ofcalcification or decreased perfusion in the cortex, which mayreflect secondary deficits due to calcification.13,14

Diagnosis of Fahr's disease is based on combinations ofclinical features, brain imaging and exclusion of other causesof intracranial calcifications.15

3. Diagnostic criteria

Diagnostic criteria of Fahr's syndrome have beenmodified andderived from Moskowitz et al. (1971), Ellie et al. (1989) andManyam (2005), and that can be stated as follows:

– Bilateral calcification of the basal ganglia visualized onneuroimaging. Other brain regions may also be observed.

– Progressive neurologic dysfunction, which generallyincludes a movement disorder and/or neuropsychiatricmanifestations. Age of onset is typically in the fourth orfifth decade, although this dysfunction may also be presentin childhood.

– Absence of biochemical abnormalities and somatic featuressuggestive of a mitochondrial or metabolic disease or othersystemic disorder.

– Absence of an infectious, toxic or traumatic cause.– Family history consistent with autosomal dominant inheri-tance.

4. Treatment

Several approaches based on diverse biological theories andsmall-scale clinical experiences have been proposed. Pharma-cological treatment should be used to improve anxiety,depression and obsessive compulsive disorder and to alleviatedystonia.16 Clonazepam and atypical antipsychotics such asquetiapine also offer a distinct advantage in treating patients

with Fahr's syndrome. Great caution is indicated when usinglithium, because it can further increase the risk of seizures inpatientswith Fahr's syndrome. Treatment strategies involvingthe use of carbamazepine, benzodiazepines and barbituratesmay exacerbate underlying gait disorders.17

5. Conclusions

1. The present paper emphasizes that diagnosis of Fahr'sdisease can be thought of in a patient presenting withneuropsychiatric manifestations along with a brain calcifi-cation pattern which is suggestive of Fahr's disease, in theabsence of biochemical abnormalities, infectious, toxic ortraumatic causes.

2. Bilateral basal ganglia calcification along with bilateralcerebellar (particularly dentate nucleus) calcificationstrongly favours the diagnosis of Fahr's disease.

3. Family history should be sought for in all such patients.4. Clonazepamand atypical antipsychotics such as quetiapine

also offer a distinct advantage in treating patients withFahr's syndrome.

Conflicts of interest

The authors have none to declare.

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[(Fig._1)TD$FIG]

Fig. 1 – CT head of Fahr's disease showing bilateral symmetrical calcification of basal ganglia, thalamus, cerebellum andfrontal cortex.

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