Brain and Development Case Reports最新文献

Background

14q12 deletion syndrome is characterized by hypotonia, postnatal microcephaly, intellectual disability, epilepsy, involuntary movements, and loss of corpus callosum. Reported cases described only the childhood period, resulting in the scarcity of information on its long-term clinical course up to adulthood.

Case presentation

We herein present a 40-year-old man with 14q12 deletion. He has never acquired head control and speech and is bedridden with spastic quadriplegia, joint contractures, scoliosis, and chorea. During the first few years, functional movements were observed, which gradually disappeared. Brain magnetic resonance imaging revealed partial hypoplasia of the corpus callosum. At 19 years, a feeding tube was placed, and at 21 years, tracheostomy was introduced due to recurrent aspiration pneumonia. Although the patient experienced tonic seizures from infancy, they disappeared at 20 years of age. Microarray comparative genomic hybridization (CGH) test at age 40 confirmed a 3.95-Mb heterozygous deletion on 14q12, encompassing FOXG1, NOVA1, C14orf23, and PRKD1. The deletion was considered to be the cause of this case.

Conclusion

The present case describes the characteristic features and long-term clinical course of a patient with 14q12 deletion syndrome. Health issues associated with dysphagia and respiration could be prominent in the mid- to late teens, and seizures may be less problematic at adulthood.

Background

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) mimics the clinical and imaging findings of small-vessel central nervous system (CNS) angiitis. An adult case of MOGAD causing right middle cerebral artery stenosis was reported in 2023. Here, we present the first reported pediatric case of left internal carotid artery stenosis in a patient with MOGAD.

Case presentation

A previously healthy 13-year-old boy presented with a two-day history of fever and headache. He experienced sudden focal-onset impaired awareness tonic seizures on the right side, with right ocular deviation. Seizure activity ceased within 5 min, but unconsciousness and paralysis of the right face and right upper extremity persisted on admission. There were no other abnormal neurological findings. Blood tests revealed mildly elevated levels of inflammatory markers. Cerebrospinal fluid examination revealed a normal protein level of 39.3 mg/dL but an elevated cell count of 154/µL and an oligoclonal band. Fluid-attenuated inversion recovery MRI sequences revealed hyperintensities in the left basal ganglia and left frontoparietal cortex. Magnetic resonance angiography revealed left internal carotid artery stenosis. Subsequently, MOGAD was diagnosed based on a positive MOG antibody test result. He received three courses of methylprednisolone pulse therapy followed by oral prednisolone for 10 weeks. His symptoms, parenchymal brain lesions, and vascular stenosis all improved with treatment.

Discussion/Conclusion

MOGAD may be associated with vascular stenosis by inducing a perivascular immune response. MOGAD may mimic CNS angiitis, including that of medium- and large-sized vessels. The presence of vascular stenosis does not rule out MOGAD.

Background

Paraneoplastic neurological syndromes (PNS) are rare in children. Unlike adults, children present with a variety of atypical neurological symptoms that are difficult to diagnose. Consequently, PNS remains an underrecognized disorder. Nevertheless, appropriate immunomodulatory therapy is crucial for neurological prognosis and should not be overlooked. We report a case in which intravenous immunoglobulin therapy effectively treated PNS while treating leukemia.

Case report

A 1.5-year-old girl with B-cell precursor acute lymphoblastic leukemia was referred to our neurology department with ptosis that developed 6 weeks after leukemia treatment and worsened over 8 days. Neurological evaluation revealed normal pupils, no ocular paralysis, no proximal muscle weakness, normal tendon reflexes, and no autonomic neuropathy. Cerebrospinal fluid and brain magnetic resonance imaging findings were normal. Antibodies against the acetylcholine receptor and P/Q-type voltage-gated calcium channels were negative. Low- and high-frequency repetitive median nerve stimulation tests revealed normal findings. We suspected PNS at the neuromuscular junction due to the persistent ptosis that occurred during leukemia treatment. Intravenous immunoglobulin therapy was effective, and ptosis disappeared after 2 weeks. The patient received standard chemotherapy for leukemia, and the ptosis did not relapse for 1 year.

Conclusion

Persistent ptosis in cancer patients requires appropriate evaluation and extensive differentiation for myasthenic syndrome. Timely treatment with immunomodulatory therapy improves neurological prognosis when PNS is suspected.

Background

Orexin is secreted in the lateral hypothalamic area and is essential for wakefulness. Impaired secretion of orexin in patients with hypothalamic lesions results in secondary hypersomnia. However, reports on the EEG features of secondary hypersomnia are limited.

Case presentation

A 16-year-old boy experienced hypersomnia, cognitive impairment, and memory deficits during maintenance treatment for an optic nerve glioma involving the optic chiasm. Brain MRI revealed that the tumor had enlarged beyond the suprasellar region and compressed the hypothalamus, midbrain, suprasellar nucleus, and basal forebrain. EEG recording during hypersomnia showed repetitive high-voltage, frontal dominant delta wave bursts regardless of whether the patient was sleeping or awake, indistinct sleep humps and spindles, and disruption of sleep architecture. Additional chemotherapy alleviated the hypersomnia, and delta wave bursts were no longer observed on EEG. Orexin levels in the cerebrospinal fluid were extremely low on admission but increased after the disappearance of hypersomnia.

Discussion and Conclusion

Hypersomnia in this case may be associated not only with impaired orexin production due to hypothalamic lesions, but also with dysfunction of the other arousal networks, including the basal forebrain and brainstem. The association between repetitive high-voltage delta wave bursts on EEG and secondary hypersomnia has not been previously described. Although the pathophysiological basis remains unclear, the damage to such multiple wake-promoting networks may be involved in the characteristic EEG finding.

Background

Neuromyelitis optica spectrum disorder (NMOSD) requires early therapeutic intervention to prevent relapse and further complications. Studies in adult patients with steroid-resistant NMOSD have indicated that the duration between disease onset and plasma exchange (PE) initiation significantly impacts prognosis, and that symptoms resolve within one month after PE in most cases. However, research assessing the prognostic factors of pediatric NMOSD is limited.

Case presentation

We report a 14-year-old boy presenting with progressive visual loss in the left eye and diagnosed with anti-aquaporin-4 antibody-positive NMOSD four months after symptom onset. As the patient proved steroid resistant, PE was performed seven times per month over a three-month period. Although his vision initially continued to deteriorate, magnetic resonance imaging indicated optic nerve lesion regression by the third month of PE. Gradual improvement in visual acuity was observed following combined maintenance treatment with prednisolone and satralizumab from three months after completing acute-phase treatment.

Conclusion

Despite the delayed initiation of PE and lack of initial response, acute-phase treatment can contribute to the recovery of visual acuity, which has significant implications, particularly in pediatric NMOSD cases.

Background

DHPRD (dihydropteridine reductase deficiency) is a very rare disorder that causes hyperphenylalaninemia (HPA), characterized by an accumulation of phenylalanine (Phe) and a profound deficit in the neurotransmitters dopamine and serotonin in the central nervous system with an alteration in folate status. It is an autosomal recessively inherited disorder caused by genetic changes in the QDPR gene.

Case presentation

A Moroccan 3-year-old girl, from a consanguineous marriage with a history of death and neurological illness in the siblings. The proband presents a very severe clinical picture; profound psychomotor delay with hypotonia, epileptic encephalopathy, abnormal movements and dysautonomia signs. The diagnosis of DHPRD was confirmed by DHPR activity assay and genetic testing. The patient was placed on a Phe-restricted diet and given augmented neurotransmitter therapy, which included levo-dopa/carbidopa, and 5-hydroxytryptophan with folinic acid. The improvement under treatment was not spectacular which is most likely due to the delay in diagnosis and management.

Discussion/conclusion

Significant advancements have been achieved in comprehending the physiopathology, the screening procedures, diagnostic techniques, treatment options, and molecular genetics pertaining to DHPRD. However, in countries where neonatal screening for phenylketonuria (PKU) is not established, severe forms of DHPRD with irreversible sequelae continue to be diagnosed. The long-term neurodevelopmental outcomes of patients with DHPRD are strongly influenced by early initiation of effective treatment; therefore, screening for PKU must be systematic and therapy should not be delayed.

Background

Forced normalization (FN) refers to the onset of psychiatric symptoms following an electroencephalogram (EEG) documented reduction in epileptic activity, cessation of clinical seizures, or both in patients with epilepsy. FN is mainly triggered by anti-seizure medication (ASM). Many ASMs have been implicated in the development of FN. However, few studies have reported perampanel (PER) induced FN.

Case report: A 10-year-old boy with a history of brain tumor resection was diagnosed with focal epilepsy based on the seizure type and EEG findings. Levetiracetam was irritable and ineffective. Lacosamide provided only partial effectiveness, leading us to prescribe PER as an add-on therapy. Approximately a week after initiating PER, the seizures resolved. However, the patient experienced concomitant emotional and cognitive instability, loss of appetite, and depression. The epileptic discharges ceased a month after starting PER, and we concluded that the FN was attributable to PER. Psychiatric symptoms gradually improved over a few months after the PER dose reduction.

Discussion

Patients with structural etiology and focal epilepsy are vulnerable to FN, putting our patients at a high risk for FN. Administration of a new ASM is the most common trigger for FN. This report is the first to describe FN induced by PER. Like other ASMs, psychiatric symptoms, seizure frequency, and EEG changes should be assessed when administering PER. Clinicians should be aware that discontinuing or reducing the dosage of the triggering medication can improve FN symptoms.

Background

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder that causes episodic hyperammonemia. Many newborns with OTCD present with nausea, delirium, lethargy, and seizure during a metabolic attack; however, brainstem failure as a complication has been rarely reported.

Case report

A 4-day-old boy developed progressive lethargy and apnea. Neurological examination when he was 5 days old revealed the absence of brainstem responses and the disappearance of systemic deep tendon reflexes with flaccid limbs, and a blood test revealed hyperammonemia (2178 µg/dL). Continuous hemodiafiltration therapy was started immediately, and whole-brainstem reflexes and systemic tendon reflexes reappeared. Subsequent genetic testing revealed a pathogenic variant of the OTC gene (p.D126G). Brain magnetic resonance imaging (MRI) at 11 days of age showed no diffuse brain edema but transient mild swelling of the basal ganglia, hyperintensity of the deep region of the paracentral sulcus and basal ganglia on T1-weighted and fluid-attenuated inversion recovery images, and symmetric restricted diffusion along the pyramidal tract. Of interest was that MRI showed no abnormalities in the brainstem other than in the cerebral peduncles.

Conclusion

This is the first detailed report of chronological recovery from brainstem dysfunction in a newborn with OTCD.

Background

Acyclovir (ACV), an antiviral drug commonly used in children, is associated with neuro- and nephron-toxicity. However, ACV neurotoxicity is mainly reported in adults and rare in children. Herein, we report the case of a boy with impaired consciousness following ACV treatment, posing challenges in differentiating posterior reversible encephalopathy syndrome (PRES) from ACV neurotoxicity. Additionally, we reviewed existing literature on ACV neurotoxicity.

Case presentation

A healthy 10-year-old boy developed severe headache and intermittent restlessness and was diagnosed with mild encephalitis/encephalopathy showing a reversible splenial lesion on magnetic resonance imaging (MRI). Since herpes simplex encephalitis could not be ruled out, ACV was initially administered. The patient later developed renal dysfunction, hypertension, and conscious disturbance. With a high serum ACV level of 14.3 μg/mL (reference; 0.4–2.0 μg/mL), we suspected PRES or ACV neurotoxicity. Upon discontinuation of ACV and starting antihypertensive therapy, the patient’s consciousness improved, leading to discharge without sequelae. In 14 pediatric cases with ACV neurotoxicity, including our case, the median age at onset was 10 years (range, 0–17 years), with renal dysfunction and high doses of ACV posing risk similar to adult cases. The mean time from ACV discontinuation to complete recovery was 5.6 ± 3.6 days, and the patients’ prognosis was good.

Conclusions

When a patient develops neurological symptoms during ACV treatment, considering the simultaneous occurrence of ACV neurotoxicity and PRES is crucial, including measuring their blood pressure, renal function, ACV levels, and MRI. Additionally, dosage should be adjusted based on ACV concentration in blood.

Background

Encephalocraniocutaneous lipomatosis (ECCL), a type of mosaic RASopathy, is a rare neurocutaneous syndrome characterized by the involvement of tissues with ectodermal and mesodermal origins, including cutaneous, ocular, and neurological abnormalities. This report presents a case of a neonate with ECCL showing rapid progression of hydrocephalus prenatally.

Case presentation

A full-term female newborn presented with head circumference enlargement and a bilateral abnormal hair pattern with alopecia at birth. Brain imaging studies showed an enlarged lateral ventricle and fatty mass in the foramen magnum, suggestive of lipomas. Ventriculoperitoneal shunting and a biopsy of the skin lesion on the head were performed on day 18. These clinical, brain imaging, and cutaneous pathological findings led to the definitive diagnosis of ECCL. Furthermore, targeted resequencing revealed an activating mosaic variant of FGFR1 in tissue samples of scalp lesions. The patient is now 2 years old with good health and normal development so far, without lipoma expansion or abnormal neurological signs and symptoms.

Conclusion

Genetic analysis of lesions is important in cases of congenital hydrocephalus with intraspinal lipoma or nevus psiloliparus. In the present case, ventriculoperitoneal shunting early in life resulted in a good neurological prognosis without lipoma expansion.