OCD at the Advent of Fahr's Disease and Small-World Connectomics: A Case Report.

Dear Editor,

Obsessive-compulsive disorder (OCD) is a disabling and chronic neuropsychiatric disorder. Disease burden for OCD ranges 1.2%–3.3%.[1,2] OCD pathophysiology is functionally correlated with basal ganglia dysfunction, particularly cortico-striato-thalamo-cortical (CSTC) circuitry. Interestingly, this CSTC basal ganglia connectome has also been implicated in brain efficiency and resilience. So, despite extensive basal ganglia insults like calcification, some patients are asymptomatic and never reach the threshold of psychopathology. On the other hand, some patients with basal ganglia calcification present with a spectrum of clinical manifestations (neurological, cognitive, and psychiatric disorders) during varied stages of insult. Attempt has been made to explain this variability by using the “small world” network concept. We are reporting a case who presented with OCD years before the onset of neurological symptoms of Fahr’s disease (recently known as Primary basal ganglia calcification [PBGC] ), in the context of “small world connectomics.”

Case Report

A 44-year-old Hindu male, a postgraduate, working as a teacher, residing in a suburban area, with anankastic traits and nil contributory family history, presented two years back (January 2019) with complaints of repeated, irrational, intrusive (ego-dystonic) thoughts and doubts about contamination; persistent, repeated washing; and low mood since 37 years of age. The reason for consultation was an increase in symptoms and dysfunction. On mental status examination, the patient had an anxious affect, obsessive doubts, compulsive acts, and grade 4 insight. Physical examination was within normal limits. The patient was diagnosed with OCD with good or fair insight (as per DSM-5). The Yale Brown Obsessive Compulsive Scale (YBOCS) score was 26. The patient was initiated on psychotherapy (12 sessions of exposure and response prevention) and pharmacotherapy (fluoxetine titrated to 80 mg). The patient reported improvement but could not follow up further due to the COVID-19 pandemic first wave crisis and defaulted treatment for a few months.

Subsequently, patient’s OCD symptoms (YBOCS: 24) recurred in the last few weeks before another visit (January 2021). The patient also complained of insidious onset of heaviness of head and limb paraesthesia. Subsequent limb stiffness and walking difficulty added to the distress. During this visit, he also reported difficulty in performing day-to-day activities such as buttoning and unbuttoning for a few days. On physical examination, the patient had increased tone in upper and lower limbs, with no other long tract signs. CT scan brain revealed calcification in bilateral basal ganglia (Figure 1). Routine blood investigations (complete blood count, sugar profile, liver function test, kidney function test) were within normal limits. Serum iPTH, calcium, magnesium, phosphorus, thyroid function, and alkaline phosphatase were within normal limits.

Figure 1.

CT Scan Brain Showing Prominent Basal Ganglia Calcification in the Lentiform Nuclei Bilaterally (Demonstrated by Yellow Arrows)

On the Extrapyramidal Symptom Rating Scale, the questionnaire score was 5, examination of Parkinsonism and akathisia score was 6, and scores on clinical global impression of Parkinsonism and severity of akathisia were 3 each. Citing recent-onset extrapyramidal symptoms and signs and abnormal neuroimaging, cognitive screening was done. Mini Mental State Examination and Montreal Cognitive Assessment scores were 29 and 28. Fluoxetine was restarted, citing prior response. Baclofen (30 mg) was initiated as per liaison with the neurology team.

Written informed consent has been obtained from the patient.

Discussion

To the best of our knowledge, this is the first case in which OCD appeared more than half a decade before the onset of neurological symptoms. Our case fulfills the clinical definition of Fahr’s disease, that is, PBGC, with neuropsychiatric and extrapyramidal disorders, and normal calcium and phosphorus metabolism. About 40% of the Fahr’s disease probands have neuropsychiatric symptoms. Initial stage of early-onset Fahr’s disease generally presents with neuropsychiatric symptoms. Unlike in our case, mood disorders are more commonly encountered at the onset of Fahr’s disease. Prior case studies have reported schizo-obsessive disorder with forbidden content and hoarding-like presentations with PBGC.[7-9] In our report, causality (as per Bradford-Hill criteria) could be concluded as “possible” based on plausibility, temporality, and specificity assessments of the association. SSRIs are reported to be associated with extrapyramidal side effects but is a remote possibility in our case (as the neurological symptoms emerged after the treatment was defaulted).

Extensive calcifications lead to reduced blood flow and have been correlated with neuropsychiatric symptoms. Moreover, these calcified deposits have been shown to drive a reactive and mild chronic inflammatory process in the basal ganglia connectome.

This phenotypic variability and progression have been explained by a model known as the “small world” network concept. By small world, we understand that brain is a highly organized functional network. Despite the loss of some nodes, the small world is able to “redistribute the lost function, with an increase in path length, with some loss of efficacy.” Studies on OCD subjects, including the ENIGMA-OCD datasets, have found significantly disrupted functional integrity and higher local clustering of the small-world top-down control network. Therefore, an insult to small-world network in Fahr’s disease at initial stages could present as OCD. This could be due to the disharmony between direct and indirect CSTC loops. Further insults would recruit or create randomness in order to manifest other phenotypes in later stages of Fahr’s disease.