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\begin{document}

\title{A Case of Close Lip Schizencephaly with absent septum pellucidum in
adult presenting with seizure disorder}



\author[1]{Chhabi Khadka}%
\author[2]{Umang  Gupta}%
\author[3]{Prakriti Bhandari}%
\author[1]{Prabin Pandey}%
\author[3]{Shailes Paudel}%
\affil[1]{National Academy of Medical Sciences}%
\affil[2]{Nepalgunj Medical College}%
\affil[3]{Patan Academy of Health Sciences}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\textbf{A Case of Close Lip Schizencephaly with absent septum pellucidum
in adult presenting with seizure disorder}

Chhabi Khadka\textsuperscript{1}, Umang Gupta\textsuperscript{2},
Prakriti Bhandari\textsuperscript{3,} Prabin Pandey\textsuperscript{1},
Shailes Paudel\textsuperscript{3}

\begin{enumerate}
\tightlist
\item
  National Academy of Medical Sciences, Nepal
\item
  Maharajgunj Medical Campus, Nepal
\item
  Patan Academy of Health Sciences, Nepal~
\end{enumerate}

\textbf{Correspondence:~}Shailes Paudel, Patan Academy of Health
Sciences, Lalitpur, Nepal

Email:
\href{mailto:shailespaudel@gmail.com}{\nolinkurl{shailespaudel@gmail.com}}

\textbf{Abstract}

Closed cleft lip with absence of the pellucid septum is a rare
congenital malformation of the brain that can be associated with a
variety of neurological conditions. We report the case of a 25-year-old
male with left hemiparesis who presented with recurrent seizures from
childhood and increased tremor. MRI brain revealed closed lip
schizencephaly with absent septum pellucidum. He had been taking
anticonvulsant for last 7 years and is under symptomatic management.

\textbf{Key Words}

Case report \textbar{} Neurosurgery \textbar{} Schizencephaly \textbar{}
Seizure Disorder \textbar{} Septum Pellucidum

\textbf{Introduction}

Schizencephaly is a rare congenital brain malformation characterized by
abnormal clefts in the cerebral cortex. Schizencephaly is rare and
thought to affect 0.54 to 1.54 out of every 100,000 live
births.\textsuperscript{1} 1.48 per 100,000 live births is the estimated
prevalence.\textsuperscript{2} Patients may present with seizures,
developmental delay, and motor deficits. Absent septum pellucidum is a
common association seen in patients with schizencephaly and has been
reported to be present in up to 50\% of
cases.\textsuperscript{3}Diagnosis is typically made through
neuroimaging studies such as MRI. We report a 25-year-old adult who has
an incidental diagnosis of schizencephaly with absent septum pellucidum.

\textbf{Case Report}

A 25-year-old male presented to the outpatient clinic with a chief
complaint of increased tremor in both upper extremities (Right
\textgreater{} Left) without any weakness. He had a history of recurrent
seizures since childhood for which he was under antiepileptic medication
(Sodium Valproate) but workup on cause of seizure was not done in the
past. Left sided weakness was present at birth which resolved as stated
by the patient. There was no significant family history of neurological
or psychiatric disorders. The patient was unemployed, a non-smoker,
non-drinker, and denied any history of recreational drug use.

On physical examination, the patient was alert and oriented, with no
signs of distress. His vital signs were within normal limits.
Neurological examination revealed high amplitude moderate frequency
resting tremor of both upper extremities with left sided weakness (Power
4/5 in both left upper and lower limb). Babinski reflex was negative
bilaterally. Considering the possibility of tremor due to Valproate,
antiepileptic regimen was changed to Levetiracetam.

MRI brain showed subtle T2 hyper intense curvilinear cleft communicating
the lateral ventricle and subarachnoid space of right fronto-parietal
convexity which is lined by closely apposed grey matter. Absence of the
septum pellucidum is noted resulting direct communication between the
lateral ventricles and squaring off of the frontal horns. (Figure 1 and
2). MR axial images through the level of optic nerve shows their normal
morphology and normal morphology of bilateral globes (Figure 3)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}
\caption{{T2W MRI axial image shows a subtle T2 hyper intense curvilinear line
(red arrow) communicating the lateral ventricle and subarachnoid space
of right fronto-parietal convexity. The black arrow denotes the absence
of the septum pellucidum resulting direct communication between the
lateral ventricles and squaring off of the frontal horns.%
}}
\end{center}
\end{figure}

\par\null

~\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}
\caption{{T1 W axial MRI image shows the abnormally located grey matter (white
arrow) lining the T2 hyper intense line.%
}}
\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}
\caption{{T2W MR axial images through the level of optic nerve shows their normal
size/ morphology and normal intensity/morphology of bilateral globes.%
}}
\end{center}
\end{figure}

The patient was started on anti-seizure medication for seizure disorder
and referred to a neurologist for further evaluation and management of
his tremor. Physical therapy was also initiated to address his left
hemiparesis and improve motor function.

\textbf{Discussion}

Schizencephaly is a rare congenital neuronal migration disorder
characterized by a cleft lined by heterotopic gray matter, which
connects the surface of the cerebral hemisphere to the lateral
ventricle.\textsuperscript{4} The term was coined by Yakovlev and
Wadsworth in 1946, based on their work on cadavers,~that classified
schizencephaly into two types.\textsuperscript{5} These are:

Type I (closed-lip): Cleft is fused, preventing CSF passage.

Type II (open-lip): A cleft is present, which permits CSF to pass
between the ventricular cavity and subarachnoid space.

Developmental delays and a variety of neurological impairments can be
linked to both kinds of schizencephaly. The etiopathogenesis of
schizencephaly remains unclear, but it may result from external factors
like middle cerebral artery stroke or genetic factors like EMX2 gene
mutation. Maternal age, substance abuse, and lack of prenatal care are
also potential risk factors. \textsuperscript{6} A related condition is
absent cavum septum pellucidum (CSP), which is characterized by the
absence or underdevelopment of the cavity between the two lateral
ventricles in the brain. In instances of closed lip schizencephaly, the
absence of CSP is a frequent finding, and it is frequently employed as a
diagnostic standard for the syndrome. With the help of several imaging
methods, such as magnetic resonance imaging (MRI), the absence of the
CSP may be shown.\textsuperscript{7} The cleft in the cerebral
hemisphere can be seen through imaging tests like an MRI, which are
commonly used to diagnose schizencephaly. Managing the neurological
abnormalities and developmental delays associated with the illness is
often treated with physical therapy, occupational therapy, and speech
therapy.\textsuperscript{8}

Also, recent research have looked at the use of fiber tractography and
diffusion tensor imaging (DTI) in the diagnosis and treatment of brain
abnormalities such schizencephaly.\textsuperscript{9} Although fiber
tractography may be used to see the route of important white matter
pathways in the brain, DTI is a type of MRI that can give information on
the microstructure of brain tissue and the integrity of white matter
tracts. These methods could offer insightful details regarding the
underlying neurological abnormalities and potential remedies for
schizencephalic patients.

DTI and fiber tractography may provide valuable information for the
diagnosis and management of these conditions, while genetic testing and
molecular profiling may help to identify underlying genetic causes and
potential treatment targets.

Some genetic mutations have been reported as possible etiological
factors for schizencephaly. The main genes identified in this regard are
COL4A1 mutations, EMX2-germline mutations, SHH gene, SIX3
gene.\textsuperscript{4}

As the precise source of the disorder is unclear, controlling its
symptoms and deficiencies serves as the mainstay of treatment.

\textbf{Conclusion}

To sum up, rare congenital brain anomalies such closed lip
schizencephaly and the missing cavum septum can cause a range of
neurological deficits and developmental delays. Like in our instance,
such deficits may come in light during maturity as a variety of
neurological symptoms. The cause of recurrent neurological symptoms
should be identified in order to determine the best treatment option and
prognosis. This should be done whenever feasible in an environment with
plenty of resources.

\textbf{Author Contribution}

\textbf{Chhabi Khadka} : Conceptualization; data curation; methodology;
writing -- original draft. \textbf{Umang Gupta} : Conceptualization;
supervision; validation; writing -- original draft; writing -- review
and editing. \textbf{Prakriti Bhandari} : Conceptualization; data
curation; validation; writing -- original draft; writing -- review and
editing. \textbf{Prabin Pandey} : Data curation; methodology;
validation; writing -- original draft; writing -- review and
editing.\textbf{Shailes Paudel} : Conceptualization; formal analysis;
supervision; validation; writing -- original draft; writing -- review
and editing

\textbf{Acknowledgements}

None.

\textbf{Funding Information}

None.

\textbf{Conflict of Interest statement}

None declared.

\textbf{Ethics Statement}

Ethical approval was not required for the case report as per the
country's guideline.

\textbf{Informed Consent}

Written informed consent was obtained from the patient to publish the
report.

\textbf{References:}

1. Hung PC, Wang HS, Chou ML, et al. Schizencephaly in children: A
single medical center retrospective study. \emph{Pediatrics \&
Neonatology} . 2018;59(6):573-580. doi:10.1016/j.pedneo.2018.01.009

2. Howe DT, Rankin J, Draper ES. Schizencephaly prevalence, prenatal
diagnosis and clues to etiology: a register-based study.\emph{Ultrasound
Obstet Gynecol} . 2012;39(1):75-82. doi:10.1002/uog.9069

3. Sundarakumar DK, Farley SA, Smith CM, Maravilla KR, Dighe MK, Nixon
JN. Absent cavum septum pellucidum: a review with emphasis on associated
commissural abnormalities. \emph{Pediatr Radiol} . 2015;45(7):950-964.
doi:10.1007/s00247-015-3318-8

4. Veerapaneni P, Veerapaneni KD, Yadala S. Schizencephaly.
In:\emph{StatPearls} . StatPearls Publishing; 2023. Accessed March 25,
2023. http://www.ncbi.nlm.nih.gov/books/NBK560913/

5. Yakovlev PI, Wadsworth RC. Schizencephalies; a study of the
congenital clefts in the cerebral mantle; clefts with fused lips.\emph{J
Neuropathol Exp Neurol} . 1946;5:116-130.
doi:10.1097/00005072-194604000-00003

6. Halabuda A, Klasa L, Kwiatkowski S, Wyrobek L, Milczarek O, Gergont
A. Schizencephaly---diagnostics and clinical dilemmas. \emph{Childs Nerv
Syst} . 2015;31(4):551-556. doi:10.1007/s00381-015-2638-1

7. Barkovich AJ. \emph{Pediatric Neuroimaging} . 4th ed. Lippincott
Williams \& Wilkins; 2005.

8. Barkovich AJ, Kjos BO, Norman D, Edwards MS. Revised classification
of posterior fossa cysts and cystlike malformations based on the results
of multiplanar MR imaging. \emph{AJR Am J Roentgenol} .
1989;153(6):1289-1300. doi:10.2214/ajr.153.6.1289

9. Berman JI, Mukherjee P, Partridge SC, et al. Quantitative diffusion
tensor MRI fiber tractography of sensorimotor white matter development
in premature infants. \emph{Neuroimage} . 2005;27(4):862-871.
doi:10.1016/j.neuroimage.2005.05.018

\textbf{Hosted file}

\verb`Original Pictures.docx`  available at \url{https://authorea.com/users/496953/articles/632445-a-case-of-close-lip-schizencephaly-with-absent-septum-pellucidum-in-adult-presenting-with-seizure-disorder}

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