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\begin{document}

\title{FAHR'S SYNDROME SECONDARY TO HYPOPARATHYROIDSM MIMICKING AS PARKINSON'S
DISEASE: A CASE REPORT}



\author[1]{Shritik Devkota}%
\author[2]{Samiksha Lamichhane}%
\author[3]{Prajjwal Pokharel}%
\author[3]{Silvia Maharjan}%
\author[4]{Kesha Meghashyam}%
\affil[1]{Anil Baghi Hospital and School of Nursing}%
\affil[2]{BP Koirala Institute of Health Sciences}%
\affil[3]{Manmohan Cardiothoracic Vascular and Transplant Center}%
\affil[4]{Glenfield Mallareddy Hospital}%


\vspace{-1em}



  
  \date{May 20, 2024}


\begingroup
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\sloppy


\textbf{INTRODUCTION:}

Fahr's disease or Fahr's syndrome is characterized by the calcification
of basal ganglia and cerebral cortex, which is usually transmitted in an
autosomal dominant manner. It is a rare neurological condition and most
of the patients with the disease condition present with movement
disorders, tremors, dyskinesia, and sometimes gait disturbances,
cognitive impairment, speech disturbances, psychiatric changes such as
mania, sensory changes or even pain \textsuperscript{{[}1-3{]}}. Fahr's
disease should be differentiated from Fahr's syndrome, which is usually
secondary to underlying systemic pathology, this could be differentiated
with blood tests for serum calcium, iPTH, along with other routine blood
investigations. Moreover, basal ganglia calcification seen in CT scans
could radiologically mimic the disease condition, thus clinical
correlation with radiological investigations are the key in the
diagnosis of Fahr's disease \textsuperscript{{[}2, 4, 5{]}.} Here, we
present a case of a 65-year-old male, with Fahr's syndrome secondary to
hyperparathyroidism which initially mimicked as Parkinson's disease and
later improved after starting the patient on vitamin D and calcium
carbonate therapy.

\textbf{CASE REPORT:}

\emph{CASE HISTORY:}

A 65-year-old male, with no previously known co-morbidities presented to
the Neurology department with the complaint of tremors, slowness of
movements and occasional postural instability for the last 1 year.
According to the patient the symptoms were gradual on progression and
was increasing in intensity for the last 1-1.5 months. Moreover, the
patient also had a recent newly developed history of headache,
generalized with no any relevant aggravating or relieving factor, along
with recurrent falls for the last 3 days. There was no history of
seizure-like activities, loss of consciousness, nausea, vomiting,
paralysis/paresis. The patient had no significant past history nor any
similar family history. The vitals were normal during the arrival to the
clinic. On clinical examination, there a positive Chvostek sign was
seen. Moreover, rigidity and narrow based gait was noted. The power,
bulk and tone were normal in all 4 limbs. There was no sensory deficit
and plantar reflex was down going.

\emph{METHODS:}

A series of laboratory investigations were sent which showed a decreased
serum calcium level of 7 mg/dL (reference range, 8.6 -- 10.2 mg/dL),
decreased serum phosphate level of 1.9 mg/dL (reference range, 3 -- 4.5
mg/dL), and a decreased parathrome level of 6.6 pg/mL (reference range,
15 -- 65 pg/mL). Detailed laboratory workup is given in Table 1.

\emph{Table 1: Blood investigation reports}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
\textbf{Investigations}\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
\textbf{Value}\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
\textbf{Reference Range}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Hemoglobin\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
12.4 gm\%\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
(13-18 gm\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Total Leucocyte Count\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
8600 /cumm\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
(4000-11000 /cumm)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Sodium/Potassium\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
136/4.3\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
(135-145 / 3.5-5.2)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
BUN/Creatinine\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
14/0.9 (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
(7-18 / 0.8-1.3 mg/dL)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
S. Calcium\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\textbf{7 mg/dL}\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
8.6-10.2 mg/dL\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
S. Phosphate\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\textbf{1.9 mg/dL}\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3-4.5 mg/dL\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Parathormone levels\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\textbf{6.6 pg/mL}\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
15-65 pg/mL\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
S. Albumin\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\textbf{3.1 mg/dL}\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
3.8-4.9 mg/dL\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\emph{Thyroid function test} fT3/fT4/TSH\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
3.01/1.31/0.755\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
(2.77-5.27 pg/mL \textbar{} 0.78-2.19 ng/dL \textbar{} 0.465-4.68
mIU/L)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
\emph{Serology} HIV 1\&2 Ag/AntiHCV Ab/HBsAg/VDRL (RPR)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
NON REACTIVE\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
NON REACTIVE\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

The patient was then subjected to radiological investigations.
Non-contrast CT of Head was done which showed symmetrical coarse
calcifications involving bilateral centrum semiovale, corona radiate,
basal ganglia (caudate nucleus and globus pallidi), pulvinar of thalami,
dentate nuclei and cerebellum (Figure 1). MRI was done which showed
changes in bilateral caudate nucleus and globus pallidi (Figure 2).

\emph{CONCLUSION AND RESULTS:}

A diagnosis of Fahr's syndrome secondary to hypoparathyroidism was made.
The patient was then started on intravenous calcium gluconate therapy
followed by oral vitamin D and calcium carbonate therapy. He was advised
to follow up in 3 months. Upon follow up on 3 months, the patient's
symptoms were clinically improving and thus the oral medications were
continued.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1: Axial sections of NCCT Head showing symmetric coarse
calcifications involving bilateral centrum semiovale (A), corona radiate
(B), basal ganglia (caudate nucleus and globus pallidi) and pulvinar of
thalami (C), dentate nuclei and cerebellum (D)

\textbf{DISCUSSION:}

Fahr's syndrome is usually a bilateral and symmetrical intra-cranial
calcification with a predilection for basal ganglia and dentate nucleus.
Moreover, primary hyperparathyroidism has been closely described in
relation with the bilateral calcific nature of Fahr's
syndrome\textsuperscript{{[}2, 5{]}}. However other causes such as
lupus, tuberous sclerosis, Alzheimer's, muscular dystrophy and
mitochondrial diseases have also been described to be the underlying
condition predisposing Fahr's syndrome \textsuperscript{{[}5, 6{]}}. The
exact prevalence of Fahr's syndrome is unknown, however it has been
incidentally detected in around 0.3-1.2\% of NCCT head
examinations\textsuperscript{{[}5{]}}. Moreover, the pathophysiology
behind Fahr's syndrome is poorly understood however anatomical and
morphological changes were seen in small vessels, perivascular regions,
neuroglia and neurons \textsuperscript{{[}7{]}}. It should be understood
that Fahr's disease exhibit clinical heterogeneity, therefore the
diagnosis should be made on the basis of neurological evidence with no
alternative explanation for symmetrical bilateral basal ganglia
calcification\textsuperscript{{[}7{]}}.

The common clinical features include headaches, seizures, and movement
disorders. Gait disturbances, dystonia, paresis, speech alterations,
dementia, tremors, chorea are other specific features seen in Fahr's
syndrome \textsuperscript{{[}2, 5{]}}. This combination of
neuropsychiatric features along with striopallidodentate calcinosis is
known as Fahr's syndrome \textsuperscript{{[}5{]}}. Similarly, the
available epidemiological data suggest higher prevalence of disease in
men with clinical features occurring around the
5\textsuperscript{th}decade of life. Severe forms of the disease leads
to severe neuropsychiatric manifestations accounting to the degrading
quality of life \textsuperscript{{[}7{]}}. Batla et al. in their review
article pointed psychiatric features, movement disorders and cognitive
impairment to be the major manifestations of Fahr's
syndrome\textsuperscript{{[}8{]}}. Moreover, Batla et al. have also
found that the evidence of basal ganglia calcification in NCCT head
could be as high as 20\%, which shall thus be differentiated with the
primary condition of Fahr's syndrome \textsuperscript{{[}2, 4, 5, 8{]}}.
Laboratory examinations should also aim for blood calcium, iPTH, and
other routine blood tests which helps in differentiation of idiopathic
Fahr's disease with Fahr's syndrome \textsuperscript{{[}5{]}}. Though CT
scans have been found to be of great importance, the role of MRI over CT
has not been well demonstrated \textsuperscript{{[}5{]}}. Though, MRI
provides a better anatomical detail than CT scan, it is less specific in
detecting calcifications. Kozic et al reported 3 individuals with
calcifications in the brain which was falsely interpreted in
MRI\textsuperscript{{[}10{]}}. Similarly, a molecular genetic pattern
testing also helps in the diagnosis of primary and secondary Fahr's
disease/syndrome; the multigene panel including \emph{PDGFB, PDGFRB,
SLC20A2, XPR1} and various other genes of interest\textsuperscript{{[}1,
8, 10, 13{]}}.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2: Axial sections of SWI sequence of MRI brain showing
susceptibility changes in bilateral caudate nucleus and globus pallidi
(dotted circles, A), dentate nuclei (curved dotted arrows, B) and
cerebellum (black, arrows, B)

Fahr's syndrome usually follows secondary to underlying pathologies such
as hypocalcemia, hypoparathyroidism, autoimmune conditions, infections,
mitochondrial diseases, infections, toxic exposures, and can be
associated with other conditions such as Cockayne syndrome, and
Aicardi-Goutieres syndrome \textsuperscript{{[}9{]}}. The primary form
is a group of primary familial brain calcification (PFBC) and a
heterogenic pathological variant has been identified in more than half
of the cases. Moreover, studies have found the chance of inheritance to
be as high as 50\% from parents to the offsprings \textsuperscript{{[}9,
10{]}}.

Management should be primarily focused in the treatment of the
underlying condition. Seizure, secondary to hypoparathyroidism could be
the primary manifestation in patients with Fahr's syndrome, yet clinical
trials have shown antiepileptic therapies have not been beneficial in
treatment in patients with such conditions \textsuperscript{{[}11{]}}.
These symptoms that are related to the Fahr's syndrome, can be treated
with vitamin D3 and steroids as well. Atypical antipsychotics are also
proven beneficial~\textsuperscript{{[}1{]}}. Moreover, there are ongoing
trials studying the effects of bisphosphonates on Fahr's disease and
syndrome \textsuperscript{{[}12{]}}.

\textbf{CONCLUSION:}

This case highlights the importance of considering Fahr's syndrome, when
the patient presents with symptoms suggestive of Parkinson's disease,
and in the presence of basal ganglia calcifications on neuroimaging.
Moreover, the diagnosis of Fahr's syndrome also highlights the
importance of blood investigations, including serum calcium and
parathyroid hormone. Early recognition and appropriate management are
crucial to prevent misdiagnosis and ensure optimal patient outcomes. The
case also underscores the necessity for a multidisciplinary approach
involving neurologists, endocrinologists, radiologists to accurately
diagnose and manage the disease condition.

\textbf{AUTHORSHIP:}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Name} & \textbf{Contribution}\tabularnewline
\midrule
\endhead
Shritik Devkota & Conceptualization, Formal analysis, Methodology,
Reviewing and editing, Resources, Investigations\tabularnewline
Samiksha Lamichhane & Conceptualization, Formal analysis, Project
Administration, Writing-Review and editing, Visualization\tabularnewline
Prajjwal Pokharel & Resources, Data Curation, Writing -- original draft,
Writing -- Review and Editing, Software, Visualization,
Methodology\tabularnewline
Silvia Maharjan & Writing-Review and Editing, Formal analysis, Data
Curation, Software\tabularnewline
Kesha Meghashyam & Supervision, Validation, Investigatons,
Writing-Review and Editing\tabularnewline
\bottomrule
\end{longtable}

\textbf{PROTECTION OF HUMANS AND ANIMALS:}

The authors declare that the procedures were followed according to the
regulations established by Clinical Research and Ethics Committee and to
the Helsinki Declaration of the World Medical Association updated in
2013.

\textbf{DATA AVAILABILITY STATEMENT:}

The datasets analyzed during the current study are available from the
corresponding author upon reasonable request. Additionally,
comprehensive literature sources used for the literature review are
cited appropriately, within the manuscript.

\textbf{FUNDING INFORMATION:}

The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to
influence the work reported in this paper.

\textbf{CONSENT:}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.

\textbf{REFERENCES:}

\begin{enumerate}
\tightlist
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\end{enumerate}\selectlanguage{english}
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\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/772287/articles/857082-fahr-s-syndrome-secondary-to-hypoparathyroidsm-mimicking-as-parkinson-s-disease-a-case-report}

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