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Article ; Online: HaNDL Syndrome: Case Report and Literature Review.

Armstrong-Javors, Amy / Krishnamoorthy, Kalpathy

2018 Volume 34, Issue 3, Page(s) 161–167

Abstract: Headache and Neurologic Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome is a rare stroke mimicker characterized by moderate to severe headache temporally associated with transient neurologic deficits, typically hemiparesis, hemisensory ... ...

Abstract	Headache and Neurologic Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome is a rare stroke mimicker characterized by moderate to severe headache temporally associated with transient neurologic deficits, typically hemiparesis, hemisensory disturbance, and/or aphasia. Cerebrospinal fluid studies reveal a lymphocytosis and elevated protein. Episodes recur over a period no longer than 3 months. Here we describe the case of a 16-year-old boy who presented with 3 episodes of self-resolving neurologic deficits, papilledema on fundoscopic examination, and leptomeningeal enhancement on magnetic resonance imaging (MRI). We additionally review the 30 previously reported pediatric cases of HaNDL syndrome, with a focus on possible etiologic and pathophysiologic mechanisms of disease. The reported case and literature review highlight the benign episodic nature of this likely underrecognized syndrome as well as the higher than expected frequency of abnormal neuroimaging findings.
MeSH term(s)	Adolescent ; Headache/diagnostic imaging ; Headache/physiopathology ; Headache/therapy ; Humans ; Lymphocytosis/cerebrospinal fluid ; Lymphocytosis/diagnostic imaging ; Lymphocytosis/therapy ; Male ; Nervous System Diseases/diagnostic imaging ; Nervous System Diseases/physiopathology ; Nervous System Diseases/therapy ; Syndrome
Language	English
Publishing date	2018-12-05
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/0883073818811546
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Article ; Online: Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma.

Bönnemann, Carsten G / Krishnamoorthy, Kalpathy S / Johnston, Jennifer J / Lee, Mary M / Fowler, Darren J / Biesecker, Leslie G / Holmes, Lewis B

American journal of medical genetics. Part A

2023 Volume 191, Issue 9, Page(s) 2337–2343

Abstract: Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant ... ...

Abstract	Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant assessed to be pathogenic or likely pathogenic was detected in the GLI3 gene in either child. This syndrome appears to be distinct from the inherited Pallister-Hall syndrome associated with GLI3 variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister-Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.
MeSH term(s)	Child ; Humans ; Pallister-Hall Syndrome/diagnosis ; Pallister-Hall Syndrome/genetics ; Hamartoma/diagnosis ; Hamartoma/genetics ; Hamartoma/pathology ; Hypothalamic Diseases/diagnosis ; Hypothalamic Diseases/genetics ; Hypothalamic Diseases/pathology ; Polydactyly/genetics
Language	English
Publishing date	2023-07-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.63306
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Article ; Online: Effect of neonatal seizure burden and etiology on the long-term outcome: data from a randomized, controlled trial.

Trowbridge, Sara K / Condie, Lois O / Landers, Jessica R / Bergin, Ann M / Grant, Patricia E / Krishnamoorthy, Kalpathy / Rofeberg, Valerie / Wypij, David / Staley, Kevin J / Soul, Janet S

Annals of the Child Neurology Society

2023 Volume 1, Issue 1, Page(s) 53–65

Abstract: Background: Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures.: ...

Abstract	Background: Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures. Methods: Neonatal seizure burden was calculated from continuous video-EEG data. Neurologic outcome was determined by standardized developmental tests and post-neonatal seizure recurrence. Results: Of 111 enrolled neonates, 43 were randomized to treatment or control groups. There were no differences in neurologic outcome between treatment and control groups. A subgroup analysis was performed for 84 neonates with acute perinatal brain injury (57 HIE, 18 stroke, 9 ICH), most of whom (70%) had neonatal seizures. There was a significant negative correlation between seizure burden and developmental scores (p<0.01). Associations between seizure burden and developmental scores were stronger in HIE and stroke groups compared with ICH (p<0.05). Conclusion: Bumetanide showed no long-term beneficial or adverse effects, as expected based on treatment duration versus duration of neonatal seizures. For neonates with perinatal brain injury, higher neonatal seizure burden correlated significantly with worse developmental outcome, particularly for ischemic versus hemorrhagic brain injury. These data highlight the need for further investigation of the long-term effects of both neonatal seizure severity and etiology.
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article
ISSN	2831-3267
ISSN (online)	2831-3267
DOI	10.1002/cns3.8
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Article ; Online: Case records of the Massachusetts General Hospital. Case 14-2014. An 11-month-old girl with developmental delay.

Krishnamoorthy, Kalpathy S / Eichler, Florian / Rapalino, Otto / Frosch, Matthew P

The New England journal of medicine

2014 Volume 370, Issue 19, Page(s) 1830–1841

MeSH term(s)	Anterior Thalamic Nuclei/pathology ; Cerebral Cortex/pathology ; Developmental Disabilities/etiology ; Diagnosis, Differential ; Fatal Outcome ; Female ; G(M2) Ganglioside ; Humans ; Infant ; Lysosomal Storage Diseases/diagnosis ; Mutation ; Reflex, Startle ; Tay-Sachs Disease/complications ; Tay-Sachs Disease/diagnosis ; Tay-Sachs Disease/genetics ; Tay-Sachs Disease/pathology
Chemical Substances	G(M2) Ganglioside (19600-01-2)
Language	English
Publishing date	2014-05-08
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcpc1305987
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Article ; Online: A 17-Year-Old Boy With High-Functioning Autism, Gastrointestinal Illness, and Seizures.

Sojar, Sakina H / Goldner, Joshua S V / Krishnamoorthy, Kalpathy / Murphy, Sarah A / Masiakos, Peter T / Klig, Jean E

Pediatrics

2018 Volume 143, Issue 1

Abstract: A healthy 17-year-old boy with a high-functioning pervasive developmental disorder presented to the emergency department after having a 4-minute episode of seizure-like activity in the setting of presumed viral gastroenteritis. Within an hour of ... ...

Abstract	A healthy 17-year-old boy with a high-functioning pervasive developmental disorder presented to the emergency department after having a 4-minute episode of seizure-like activity in the setting of presumed viral gastroenteritis. Within an hour of emergency department arrival, he developed a forehead-sparing facial droop, right-sided ptosis, and expressive aphasia, prompting stroke team assessment and urgent neuroimaging. Laboratory results later revealed a serum sodium of 119 mmol/L. Neurologic deficits self-resolved, and a full physical examination revealed diffuse abdominal tenderness in the lower abdomen with rebound tenderness in the right-lower quadrant. The patient was admitted to the PICU for electrolyte management and monitoring. A computed tomography (CT) scan of the abdomen obtained the following morning revealed the patient's final diagnosis.
MeSH term(s)	Abdominal Pain/complications ; Abdominal Pain/diagnostic imaging ; Abdominal Pain/surgery ; Adolescent ; Appendicitis/complications ; Appendicitis/diagnostic imaging ; Appendicitis/surgery ; Autistic Disorder/complications ; Autistic Disorder/diagnostic imaging ; Autistic Disorder/surgery ; Gastroenteritis/complications ; Gastroenteritis/diagnostic imaging ; Gastroenteritis/surgery ; Humans ; Male ; Seizures/complications ; Seizures/diagnostic imaging ; Seizures/surgery
Language	English
Publishing date	2018-12-13
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2017-3964
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Um IV Zs.131: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 357: Show issues

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Article ; Online: A Pilot Randomized, Controlled, Double-Blind Trial of Bumetanide to Treat Neonatal Seizures.

Soul, Janet S / Bergin, Ann M / Stopp, Christian / Hayes, Breda / Singh, Avantika / Fortuno, Carmen R / O'Reilly, Deirdre / Krishnamoorthy, Kalpathy / Jensen, Frances E / Rofeberg, Valerie / Dong, Min / Vinks, Alexander A / Wypij, David / Staley, Kevin J

Annals of neurology

2020 Volume 89, Issue 2, Page(s) 327–340

Abstract: Objective: In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy ... ...

Abstract	Objective: In the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group. Methods: A randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures. Results: Subjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post-SDA (both p < 0.01) compared with 2-hour baseline in treatment versus control groups with adjustment for seizure burden. Interpretation: Although definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327-340.
MeSH term(s)	Anticonvulsants/therapeutic use ; Bumetanide/therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Electroencephalography ; Female ; GABA Modulators/therapeutic use ; Genetic Diseases, Inborn/complications ; Humans ; Hypoxia-Ischemia, Brain/complications ; Infant, Newborn ; Intracranial Hemorrhages/complications ; Male ; Meningoencephalitis/complications ; Nervous System Malformations/complications ; Phenobarbital/therapeutic use ; Pilot Projects ; Seizures/drug therapy ; Seizures/etiology ; Sodium Potassium Chloride Symporter Inhibitors/therapeutic use ; Stroke/complications
Chemical Substances	Anticonvulsants ; GABA Modulators ; Sodium Potassium Chloride Symporter Inhibitors ; Bumetanide (0Y2S3XUQ5H) ; Phenobarbital (YQE403BP4D)
Language	English
Publishing date	2020-12-03
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.25959
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Zs.A 1370: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 478: Show issues

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Article: Paroxysmal non-epileptic events resembling seizures in children with otitis media.

Soman, Teesta B / Krishnamoorthy, Kalpathy S

Clinical pediatrics

2005 Volume 44, Issue 5, Page(s) 437–441

Abstract: Children may frequently present with recurrent spells, which are often thought to be seizures. However, there are several benign non-epileptic conditions that mimic seizures. A group of 8 children is described who were diagnosed with otitis media and ... ...

Abstract	Children may frequently present with recurrent spells, which are often thought to be seizures. However, there are several benign non-epileptic conditions that mimic seizures. A group of 8 children is described who were diagnosed with otitis media and presented with recurrent, stereotypic spells suggestive of seizures. A paroxysmal phenomenon, in association with otitis media, resembling seizures, has not been previously described. These paroxysmal phenomena resembling seizures may be related to acute otitis media and should be included in the differential diagnosis of paroxysmal non-epileptic events in infants and young children.
MeSH term(s)	Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Cohort Studies ; Diagnosis, Differential ; Electroencephalography ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Otitis Media/complications ; Otitis Media/diagnosis ; Otitis Media/drug therapy ; Risk Assessment ; Seizures/diagnosis ; Seizures/etiology ; Seizures, Febrile/diagnosis ; Seizures, Febrile/etiology ; Severity of Illness Index ; Treatment Outcome
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2005-06
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	207678-0
ISSN	1938-2707 ; 0009-9228
ISSN (online)	1938-2707
ISSN	0009-9228
DOI	10.1177/000992280504400509
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Article ; Online: The probability of seizures during continuous EEG monitoring in high-risk neonates.

Worden, Lila T / Chinappen, Dhinakaran M / Stoyell, Sally M / Gold, Jacquelyn / Paixao, Luis / Krishnamoorthy, Kalpathy / Kramer, Mark A / Westover, Michael B / Chu, Catherine J

Epilepsia

2019 Volume 60, Issue 12, Page(s) 2508–2518

Abstract: Objective: We evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol.: Methods: ...

Abstract	Objective: We evaluated the impact of monitoring indication, early electroencephalography (EEG), and clinical features on seizure risk in all neonates undergoing continuous EEG (cEEG) monitoring following a standardized monitoring protocol. Methods: All cEEGs from unique neonates 34-48 weeks postmenstrual age monitored from 1/2011-10/2017 (n = 291) were included. We evaluated the impact of cEEG monitoring indication (acute neonatal encephalopathy [ANE], suspicious clinical events [SCEs], or other high-risk conditions [OHRs]), age, medication status, and early EEG abnormalities (including the presence of epileptiform discharges and abnormal background continuity, amplitude, asymmetry, asynchrony, excessive sharp transients, and burst suppression) on time to first seizure and overall seizure risk using Kaplan-Meier survival curves and multivariable Cox proportional hazards models. Results: Seizures occurred in 28% of high-risk neonates. Discontinuation of monitoring after 24 hours of seizure-freedom would have missed 8.5% of neonates with seizures. Overall seizure risk was lower in neonates monitored for ANE compared to OHR (P = .004) and trended lower compared to SCE (P = .097). The time course of seizure presentation varied by group, where the probability of future seizure was less than 1% after 17 hours of seizure-free monitoring in the SCE group, but required 42 hours in the OHR group, and 73 hours in the ANE group. The presence of early epileptiform discharges increased seizure risk in each group (ANE: adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.23-15.13, P = .022; SCE: aHR 10.95, 95% CI 4.77-25.14, P < 1e-07; OHR: aHR 56.90, 95% CI 10.32-313.72, P < 1e-05). Significance: Neonates who undergo cEEG are at high risk for seizures, and risk varies by monitoring indication and early EEG findings. Seizures are captured in nearly all neonates undergoing monitoring for SCE within 24 hours of cEEG monitoring. Neonates monitored for OHR and ANE can present with delayed seizures and require longer durations of monitoring. Early epileptiform discharges are the best early EEG feature to predict seizure risk.
MeSH term(s)	Electroencephalography/methods ; Electroencephalography/trends ; Female ; Humans ; Infant, Newborn ; Male ; Predictive Value of Tests ; Risk Factors ; Seizures/diagnosis ; Seizures/physiopathology
Language	English
Publishing date	2019-11-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.16387
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Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Chiari malformations: An important cause of pediatric aspiration.

Fuller, Jennifer C / Sinha, Sumi / Caruso, Paul A / Hersh, Cheryl J / Butler, William E / Krishnamoorthy, Kalpathy S / Hartnick, Christopher J

International journal of pediatric otorhinolaryngology

2016 Volume 88, Page(s) 124–128

Abstract: Chronic aspiration poses a major health risk to the pediatric population. We describe four cases in which work up for chronic aspiration with a brain MRI revealed a Chiari I malformation, a poorly described etiology of pediatric aspiration. All patients ... ...

Abstract	Chronic aspiration poses a major health risk to the pediatric population. We describe four cases in which work up for chronic aspiration with a brain MRI revealed a Chiari I malformation, a poorly described etiology of pediatric aspiration. All patients had at least one non-specific neurologic symptom but had swallow studies more characteristic of an anatomic than a neurologic etiology. Patients were referred to neurosurgery and underwent posterior fossa decompression with symptom improvement. A high index of suspicion for Chiari malformation should be maintained when the standard work up for aspiration is non-diagnostic, particularly when non-specific neurologic symptoms are present.
MeSH term(s)	Arnold-Chiari Malformation/complications ; Arnold-Chiari Malformation/diagnostic imaging ; Arnold-Chiari Malformation/surgery ; Child, Preschool ; Decompression, Surgical ; Female ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neurosurgical Procedures ; Recurrence ; Respiratory Aspiration/etiology ; Treatment Outcome
Language	English
Publishing date	2016-09
Publishing country	Ireland
Document type	Case Reports ; Journal Article
ZDB-ID	754501-0
ISSN	1872-8464 ; 0165-5876
ISSN (online)	1872-8464
ISSN	0165-5876
DOI	10.1016/j.ijporl.2016.06.019
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Article: Magnetic resonance imaging evaluation of possible neonatal sinovenous thrombosis.

Eichler, Florian / Krishnamoorthy, Kalpathy / Grant, P Ellen

Pediatric neurology

2007 Volume 37, Issue 5, Page(s) 317–323

Abstract: There are few data on magnetic resonance imaging findings in newborns for whom there is a concern for cerebral sinovenous thrombosis. The study objective was to document findings on magnetic resonance imaging or magnetic resonance venography in cases of ... ...

Abstract	There are few data on magnetic resonance imaging findings in newborns for whom there is a concern for cerebral sinovenous thrombosis. The study objective was to document findings on magnetic resonance imaging or magnetic resonance venography in cases of suspected neonatal sinovenous thrombosis. A retrospective search of the institutional database was performed to find neonates whose cranial computed tomography raised the suspicion for thrombus. Documented abnormalities were detected on magnetic resonance venography, diffusion-weighted imaging, and T(2)-weighted imaging. Of 15 neonates with suspicious computed tomography studies, 2 had a definite intraluminal clot in the deep venous system; the remainder showed decreased flow-related enhancement within the dural venous sinuses. In all these cases, the sinus was compressed by adjacent subdural hematoma or sutural diastasis. Of the 15 patients, 5 had parenchymal abnormalities (2 of these had definite intraluminal clot). Parenchymal abnormalities were classified as hemorrhage (3/5), cytotoxic edema (3/5), or vasogenic edema (1/5). Intraluminal clot in the newborn is more often identified in the deep than in the superficial venous system. With evidence of venous injury in the absence of identified thrombus, it is possible that either clots dissolve quickly, escaping detection, or that the superficial venous system is vulnerable to mechanical forces during delivery.
MeSH term(s)	Evaluation Studies as Topic ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Pregnancy ; Retrospective Studies ; Sinus Thrombosis, Intracranial/diagnosis ; Tomography, X-Ray Computed
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639164-3
ISSN	1873-5150 ; 0887-8994
ISSN (online)	1873-5150
ISSN	0887-8994
DOI	10.1016/j.pediatrneurol.2007.06.018
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