Hypothalamic hamartoma (HH), or tuber cinereum hamartoma is a congenital malformation with an incidence of 1-2 per 100,000 [1]. This tumor-like lesion is situated in the tuber cinereum of the hypothalamus in the region of the optic chiasma and mammillary bodies. Usually, HH is observed as an isolated lesion, although cases in association with Pallister-Hall syndrome have also been reported [2].

The clinical presentation of HH is variable but is associated with gelastic seizures, visual dysfunction, early onset puberty and neuropsychiatric impairment [3]. The onset of symptoms is as early as the 2nd or 3rd year of life and progresses over the years.

Gelastic seizures occur in neonates and children, last for 2 to 30 seconds and are characterized by uncontrollable laughter with recurrent seizures without loss of consciousness. The prevalence of these seizures is 1 in 200,000 [4]. Rarely, status gelasticus can also occur [5]. Subsequently, the patients may develop other types of seizures like myoclonic, tonic or generalized [6]. Cognitive and neuropsychiatric symptoms are seen only in cases of HH with epilepsy [7] [8]. These include delayed development, cognitive dysfunction, and rage.

Early onset puberty is a typical clinical feature of large, pedunculated HH [9] [10] and can be observed even in children under the age of 3 years. It is seen in 40% of HH patients with seizures.

• Epilepsy

  In 1988, Berkovic and colleagues described 4 children with hypothalamic hamartoma, treatment-resistant epilepsy, and progressive neurobehavioral deficits, providing the first definitive description of the catastrophic epilepsy syndrome that we recognize [medlink.com]

  A lateral slowing and epileptiform features in interictal EEG can be observed in progressive epilepsy followed by seizure specific features like bilateral synchronous or generalized activity when other types of epilepsy develop. [symptoma.com]

  Previous reports of gelastic epilepsy have usually involved only isolated cases. [pediatricneurologybriefs.com]

  In this paper, 14 adult patients with hypothalamic hamartoma and epilepsy, of whom three developed epilepsy only in adult life, are presented. [ncbi.nlm.nih.gov]

• Precocious Puberty

  Central precocious puberty is associated with hypothalamic hamartoma lesions that attach anteriorly to the ventral hypothalamus, near the tuber cinereum and pituitary stalk. [medlink.com]

  Albright AL Lee PA : Neurosurgical treatment of hypothalamic hamartomas causing precocious puberty. J Neurosurg 78 : 77 – 82 1993 Albright AL Lee PA: Neurosurgical treatment of hypothalamic hamartomas causing precocious puberty. [thejns.org]

  Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. [ncbi.nlm.nih.gov]

  Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. Conclusions. [doi.org]

• Pallister-Hall Syndrome

  Hypothalamic hamartomas are rare tumors that typically present in childhood, often with gelastic seizures, precocious puberty, or as a manifestation of Pallister-Hall syndrome. [ncbi.nlm.nih.gov]

  Squires LA, Constantini S, Miller DC, Wisoff JH: Hypothalamic hamartoma and the Pallister-Hall syndrome. Pediatr Neurosurg 1995;22:303–308. Thomas HM, Todd PJ, Heaf D, Fryer AE: Recurrence of Pallister-Hall syndrome in two sibs. [karger.com]

  Usually, HH is observed as an isolated lesion, although cases in association with Pallister-Hall syndrome have also been reported. [symptoma.com]

• Disability

  The Childrens and Families Act 2014 Special Educational Needs and Disability Code of Practice: 0 to 25 years Benefits and Financial Support HH can present varying types of disability on which can impact on a family, if looking after a child or just be [hhugs-uk.com]

  The presence of aggression significantly correlated with 1) male gender, 2) younger age at time of first seizure onset, 3) the presence of intellectual disability, and 4) the presence of multiple seizure types (versus gelastic seizures only). [ncbi.nlm.nih.gov]

  The second syndrome consists of the neurologic symptoms, usually beginning with gelastic (laughing) seizures, but often progressing to additional, more disabling seizure types, along with cognitive impairment and behavioral symptoms. [medlink.com]

  Learn More 1 in 200k diagnosed worldwide Often goes undiagnosed or misdiagnosed for years Seizures commonly unresponsive to medication Can result in cognitive and behavioral deterioration, learning disabilities, endocrine dysfunction and sleep disturbances [hopeforhh.org]

  Symptoms often begin in early infancy and are progressive, often with general cognitive and functional disability. Lesions can cause gelastic seizures, visual problems, early onset of puberty and behavioral problems 3. [radiopaedia.org]

• Surgical Procedure

  For such patients minimally invasive surgical procedures, or medical therapy should be considered. [ncbi.nlm.nih.gov]

  Niigata Japan, We established a surgical procedure using magnetic resonance imaging (MRI)-guided stereotactic radiofrequency thermocoagulation (SRT) for epileptogenic hypothalamic hamartomas over 15 years ago in Epilepsy Center, Nishi-Niigata Chuo National [masa.go.jp]

  Wait determined that treatment would include two surgical procedures. "Our immediate goal was not to remove all of the growth, but to disconnect it from his brain so that the seizures would stop," said Dr. Wait. "This was a two-stage approach. [cnsa.com]

  […] of an HH is the only surgical procedure that has a significant chance of reversing precocious puberty, and for pedunculated HH, total removal can be accomplished safely. [doi.org]

• Overeating

  The onset of symptoms is as early as the 2nd or 3rd year of life and progresses over the years. [symptoma.com]

  Abstract The prognosis for patients with hypothalamic hamartoma has improved dramatically over the last 20 years, for 3 main reasons. [ncbi.nlm.nih.gov]

• Tachycardia

  Transient central hyperthermia, hypertension, and tachycardia were observed during the coagulation procedure. Intra-hamartoma spikes and slow waves were identified on depth electrode recordings. No gelastic seizure was induced by deep stimulation. [ncbi.nlm.nih.gov]

  Transient central hyperthermia, hypertension, and tachycardia were observed during the coagulation procedure. No gelastic seizure was induced by deep stimulation. [cnjournal.biomedcentral.com]

  It is usually accompanied by autonomic signs (tachycardia, breathing disorders, flushing, pupil dilation, etc.). 7–9 Some patients experience gelastic and dacrystic (crying) seizures at the same time. [elsevier.es]

• Flushing

  Seizures were frequent (several/day) and characterized by laughing attacks, sometimes with facial flushing, and rarely with loss of contact. Age at onset was less than a year in 3, and < 12 years in 8. [pediatricneurologybriefs.com]

  Dacrystic episodes presented in clusters at sleep onset, initially in the form of moaning followed by face-flushing that rapidly evolved to crying, associated with a lateral and upper deviation of both eyeballs, along with clonic aspects of the eyelids [ncbi.nlm.nih.gov]

  Patients having these seizures may exhibit groaning and flushing, followed soon after by crying. [elsevier.es]

• Hunger

  Hypothalamic hamartoma: A benign tumor of the hypothalamus, the area of the brain that controls body temperature, hunger, and thirst. [medicinenet.com]

  The hypothalamus is located at the base of the brain and controls many of the basic functions of life such as hunger, aggression, sexual drive, growth, hormonal development, body temperature and salt and water metabolism. [northwell.edu]

  Functions of the hypothalamus can be listed as: controls the release of 8 major hormones by the pituitary gland controls body temperature control of food and water intake, hunger and thirst control of sexual behavior and reproduction control of daily [news-medical.net]

  The hypothalamus is located at the base of the brain and regulates many of the “automatic” functions of the brain, including hunger, thirst, temperature, passion, and hormone regulation. It’s also involved in hormone balance. [epilepsy.com]

  Periodic disorders. 28.1 Kleine-Levin syndrome (periodic somnolence and morbid hunger). 28.2 Spontaneous periodic fever, hypothermia, Shapiro syndrome and periodic Cushing's syndrome. 28.3 Acute intermittent porphyria. 28.4 Narcolepsy. 28.5 Epileptic [elsevier.com]

• Seizure

  An electroencephalogram (EEG) is performed in all HH patients with seizures. It may be normal in very young children with gelastic seizures but is usually abnormal in older HH patients who develop other types of seizures. [symptoma.com]

  The second syndrome consists of the neurologic symptoms, usually beginning with gelastic (laughing) seizures, but often progressing to additional, more disabling seizure types, along with cognitive impairment and behavioral symptoms. [medlink.com]

  Seizure outcome was scored according to Engel's classification. Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. [ncbi.nlm.nih.gov]

• Encephalopathy

  Surgical ablation of HH can reverse epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery seem to be useful and safe approaches for treatment, in particular of small HH. [ncbi.nlm.nih.gov]

• Convulsions

  We report a case of hypothalamic hamartoma in an adult female who presented with gelastic seizures, generalized convulsions, and ictal aggressive psychotic behavior. Anticonvulsant treatment was ineffective in controlling the epileptic seizures. [ncbi.nlm.nih.gov]

  Convulsions, mental retardation, or behavioral disorders were present in 48% of the cases; 36% had precocious puberty. ( Am J Dis Child 1983;137:127-133) [jamanetwork.com]

  Grace’s stare is unfocused, her giggle jerky and her breathing convulsed. Still, to the untrained eye, it looks like an adorable quirk, not the fingerprint of a massive tumor. [nytimes.com]

  Treatment to date has revolved around the use of anti-convulsant medications. This has led to disappointing results and surgical options have been explored. [my.clevelandclinic.org]

• Atonic Seizures

  Generalized convulsions (involuntary shaking, twitching, and disorganized movements) Drop or atonic seizures (brief loss of muscle tone leading to falls) In this stage, your child may display signs of progressive cognitive impairment, worsening school [barrowneuro.org]

  Children may also have other types of seizures, either immediately after these gelastic seizures or at other times. These include tonic-clonic and atonic seizures. [epilepsy.org.uk]

  He had also history of infantile spasms and atonic seizures since a similar period. Seizures responded poorly to antiepileptic treatment. [annalsofian.org]

  Simple partial seizures were the most common, followed by complex partial seizures and generalised seizures (in some cases). Atonic seizures were only present in 1 patient. [elsevier.es]

The workup in HH depends on neuroimaging with magnetic resonance imaging (MRI) being the gold standard for confirming or excluding the diagnosis. However, it is difficult to perform due to interference with motion artifacts and also because it could be normal in some of the patients. Computed tomograms are associated with radiation exposure (especially important in small children) and are also unable to detect small HH.

History and physical examination, especially by an endocrinologist are essential in children with early onset puberty. Laboratory tests for reproductive hormone levels along with levels of adrenal, growth hormone and thyroid hormone are indicated in these children.

An electroencephalogram (EEG) is performed in all HH patients with seizures. It may be normal in very young children with gelastic seizures but is usually abnormal in older HH patients who develop other types of seizures. A lateral slowing and epileptiform features in interictal EEG can be observed in progressive epilepsy [11] followed by seizure specific features like bilateral synchronous or generalized activity when other types of epilepsy develop [12].

Findings of HH on MRI are non-enhancing lesions with 93% being hyperintense on T2 and 74% being hypointense on T1 weighted images [13]. Morphologically, HH can be classified as sessile, broad-based or pedunculated [2] [3]. Sessile HH is connected to the mammillary bodies, causing their distortion and displacement, if large [2] Pedunculated HH extend into the suprasellar space and are attached to the tuber cinereum.

Neuropsychological tests help to evaluate the memory, language skills and ability of the patients to solve problems as HH patients with epilepsy often suffer from progressive developmental and cognitive deficits. The tests also are useful to plan treatment and record improvement (after therapy and surgery) or deterioration over time.

• Hypsarrhythmia

  These patients may have hypsarrhythmia on initial EEG, and may respond to ACTH treatment with improvement of IS. However, all became refractory with other seizure types, more commonly seen in HH patients. [ncbi.nlm.nih.gov]

Treatment should be individualized to the patient's clinical course and the surgical anatomy of the hypothalamic hamartoma. [medlink.com]

No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. [ncbi.nlm.nih.gov]

The duration of treatment varied from 2.66 to 8.41 years. [doi.org]

This technique may prove useful for diagnosis, prognosis and treatment planning, as well as to guide transendoscopic therapeutic interventions for HH. [ncbi.nlm.nih.gov]

Categorizing HHs by the degree of hypothalamic involvement has contributed to the accurate prediction of their prognosis and to improved treatment strategies. [jstage.jst.go.jp]

The prognosis is usually poor, the GS evolving into symptomatic generalized epilepsy and leading to cognitive deterioration, but early recognition and surgical ablation of the hamartoma may occasionally result in control of drug refractory seizures and [pediatricneurologybriefs.com]

Only 1 patient was not effectively treated ( CONCLUSIONS: Patients with Lennox-Gastaut syndrome symptomatic to hypothalamic hamartomas have better postsurgical outcome due to other etiologies compared with cryptogenic and symptomatic Lennox-Gastaut syndrome [ncbi.nlm.nih.gov]

The etiology of this anomaly and the pathogenesis of its peculiar symptoms remain unclear, but recent electrophysiological, neuroimaging, and clinical studies have yielded important data. [jstage.jst.go.jp]

This is the leading international professional reference text that also serves as a bench book, describing all aspects of the pathology of brain tumours - genetics, molecular biology, epidemiology, morphology, immunohistochemistry, diagnostic criteria [books.google.de]

More recent epidemiologic studies have found these associations to be less consistent, with gelastic epilepsy predominant in the majority of patients regardless of morphology. [en.wikipedia.org]

Results Epidemiological and perinatal data ( Table 1 ) Of the 10 patients in our series, 6 were male. Only one patient had a family history of epilepsy. [elsevier.es]

First, because of improved understanding of the anatomy and pathophysiology of these varied lesions.Second, due to advances in brain imaging and refinements in microsurgery, including the anterior transcallosal interforniceal approach, endoscopic, and [ncbi.nlm.nih.gov]

This review of hypothalamic hamartomas presents current classifications, pathophysiologies, and treatment modalities. [jstage.jst.go.jp]

The accumulation of knowledge regarding the pathogenesis of symptoms and the development of safe, effective treatment modalities may lead to earlier intervention in young HH patients and prevent the decline in their cognitive abilities and quality of [jstage.jst.go.jp]

[…] prognosis is usually poor, the GS evolving into symptomatic generalized epilepsy and leading to cognitive deterioration, but early recognition and surgical ablation of the hamartoma may occasionally result in control of drug refractory seizures and prevention [pediatricneurologybriefs.com]

Generally, AEDs (Antiepileptic drugs) are ineffective for GSs associated with HH and rarely prevent cognitive and behavioral deterioration. [spandidos-publications.com]

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