Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures.

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.

Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation for the Treatment of Chronic Intractable Pain Originating From a Lipofibromatous Hamartoma of the Median Nerve.

This case report presents an application of peripheral nerve stimulation to the median nerve to treat a patient with intractable pain due to a lipofibromatous hamartoma of the left upper extremity. Ultra high-frequency ultrasound was used to determine the boundaries of the hamartoma. The patient then underwent an ultrasound-guided implantation of 2 stimulator electrodes distal to the elbow along the median nerve with stimulation coverage achieved at 1.2 and 1.4 mA, respectively. After an uneventful procedure, the pain score immediately decreased from 9 out of 10 to less than 6 on a numeric rating scale. Two weeks after the procedure, the patient reported substantial pain relief, with an average pain level of 5 to 6 out of 10. Twelve months after implantation, the patient maintained significant pain relief, rating her average pain level as a 4 to 6 out of 10. Placement of a percutaneous peripheral nerve stimulator was safe and effective with no adverse events being reported at the 12-month follow-up.

Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording.

OBJECTIVE: Ablation surgery has become the first line of treatment for hypothalamic hamartomas (HHs). For effective treatment, optimum targeting of ablation is mandatory. The present study aimed to evaluate the correspondence between the electrophysiological features of HHs and morphological targeting by semimicrorecording during stereotactic radiofrequency thermocoagulation (SRT). METHODS: Eighty HH patients who underwent SRT were involved. Semimicrorecording was performed on the first trajectory. The distance from the center of the target at the morphological border (TMB) determined by magnetic resonance imaging, differences in discharge patterns, and area potentials (APs) were measured. RESULTS: The electrophysiological border (EB) between the HH and hypothalamus was detected by semimicrorecording in 73 (91.3%), AP increase (API) in the HH was detected in 31 (38.8%), and spike discharges (SDs) of the HH were detected in 56 patients (70.0%). Semimicrorecording showed significantly different APs among structures passing through the trajectory, except between API and SDs. The median distances from the center of the TMB to the EB, API, SDs, and AP decline were -3.50, -2.49, -1.38, and +2.00 mm, respectively. SIGNIFICANCE: The electrophysiological features of HHs were shown by semimicrorecording during SRT. The EB corresponded to the morphological border. The electrophysiologically active area of HHs was located near the border. Ablation surgery should focus on disconnection at the border between the HH and the hypothalamus to maximize its effectiveness, as well as to reduce complications.

Outcome of incidentally detected airway nodules.

Low-dose chest computed tomography (LDCT) screening increased detection of airway nodules. Most nodules appear to be secretions, but pathological lesions may show similar findings. The National Comprehensive Cancer Network (NCCN) recommends repeating LDCT after 1 month and proceeding to bronchoscopy if the nodules persist. However, no reports exist about incidentally detected airway nodules. We investigated the significance of airway nodules detected by LDCT screening.We screened patients with incidental airway nodules detected by LDCT in the Seoul National University Hospital group. The characteristics of computed tomography, bronchoscopy, pathology and clinical findings were analysed.Among 53 036 individuals who underwent LDCT screening, 313 (0.6%) had airway nodules. Of these, 186 (59.4%) were followed-up with chest computed tomography and/or bronchoscopy. Seven (3.8%) cases had significant lesions, including leiomyoma (n=2), endobronchial tuberculosis (n=2), chronic inflammation (n=1), hamartoma (n=1) and benign granuloma (n=1). The remaining 179 lesions were transient, suggesting that they were secretions.The use of LDCT for lung cancer screening demonstrated the low incidence of airway lesions. Most lesions were transient secretions. True pathological lesions were rare, and no malignant lesion was found. The current recommendation of the NCCN guideline is a reasonable approach that can avoid unnecessary bronchoscopy.

Asymptomatic Interhypothalamic Adhesions in Children.

With the use of high-resolution MR imaging techniques, we have increasingly observed anomalies of the hypothalamus characterized by a band of tissue spanning the third ventricle between the hypothalami, often without associated clinical sequelae. Historically, hypothalamic anomalies are highly associated with symptoms referable to a hypothalamic hamartoma, midline congenital disorder, hypothalamic-pituitary dysfunction, or seizures, with very few asymptomatic patients reported. The interhypothalamic tissue described in our cohort was observed incidentally through the routine acquisition of high-resolution T1WI. No referable symptoms were identified in most of the study group. In the appropriate patient population in which associated symptoms are absent, the described hypothalamic anomalies may be incidental and should not be misdiagnosed as hypothalamic hamartomas.

Surgical Outcomes in a Large, Clinical, Low-Dose Computed Tomographic Lung Cancer Screening Program.

BACKGROUND: Lung cancer screening with low-dose computed tomography is proven to reduce lung cancer mortality among high-risk patients. However, critics raise concern over the potential for unnecessary surgical procedures performed for benign disease as a result of screening. We reviewed our outcomes in a large clinical lung cancer screening program to assess the number of surgical procedures done for benign disease, as we believe this is an important quality metric. METHODS: We retrospectively reviewed our surgical outcomes of consecutive patients who underwent low-dose computed tomography lung cancer screening from January 2012 through June 2014 using a prospectively collected database. All patients met the National Comprehensive Cancer Network lung cancer screening guidelines high-risk criteria. RESULTS: There were 1,654 screened patients during the study interval with clinical follow-up at Lahey Hospital & Medical Center. Twenty-five of the 1,654 (1.5%) had surgery. Five of 25 had non-lung cancer diagnoses: 2 hamartomas, 2 necrotizing granulomas, and 1 breast cancer metastasis. The incidence of surgery for non-lung cancer diagnosis was 0.30% (5 of 1,654), and the incidence of surgery for benign disease was 0.24% (4 of 1,654). Twenty of 25 had lung cancer, 18 early stage and 2 late stage. There were no surgery-related deaths, and there was 1 major surgical complication (4%) at 30 days. CONCLUSIONS: The incidence of surgical intervention for non-lung cancer diagnosis was low (0.30%) and is comparable to the rate reported in the National Lung Screening Trial (0.62%). Surgical intervention for benign disease was rare (0.24%) in our experience.

Ictogenesis and symptomatogenesis of gelastic seizures in hypothalamic hamartomas: an ictal SPECT study.

PURPOSE: To topographically localize the ictogenic zone within hypothalamic hamartomas (HHs) and the symptomatogenic zone for gelastic seizure (GS), we analyzed data from both interictal and ictal single photon emission computed tomography (SPECT). METHODS: Ictal SPECT was performed immediately after GS onset in 21 patients with HH (aged 2-36 years, mean 13.8 years) who underwent stereotactic radiofrequency thermocoagulation (SRT). SPECT data were statistically analyzed by means of subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) and statistical parametric mapping (SPM). Topographic localization of ictal hyperperfusion areas was evaluated. RESULTS: SISCOM obtained in 27 studies demonstrated ictal hyperperfusion in the HH interface zone in 16 studies of 13 patients (hot HH group). In these patients, HHs were significantly larger than those without hyperperfusion of HH in 11 studies of 8 patients (21.4 ± 10.3 vs. 12.3 ± 7.3 mm in diameter, p < 0.05, t-test). In all patients and in the hot HH group, SPM group analysis of individual differences between interictal and ictal data revealed significantly (p < 0.001) hyperperfused areas in the ipsilateral hypothalamus, mediodorsal (MD) nucleus of the thalamus and putamen, bilateral pontine tegmentum, and contralateral inferior semilunar lobule of the cerebellum. There was no hyperperfusion in the mammillothalamocingulate pathway. DISCUSSION: The present study confirmed that ictogenesis occurs in the HH interface zone, which should accordingly be the target for SRT. We suggest that a thalamopontocerebellar circuit plays an important role for stereotypical and automatic symptomatogenesis of GS and that the hypothalamus and MD nucleus of the thalamus are potentially involved in epileptic encephalopathy.

Positron emission tomography with glucose hypermetabolism of a hypothalamic hamartoma in infantile spasms associated with Pallister-Hall syndrome.

Although hypothalamic hamartomas (HHs) have been shown to be intrinsically epileptogenic and to participate in the generation of gelastic seizures, no evidence has been reported regarding its contribution to the pathogenesis of infantile spasms. We describe a male infant with Pallister-Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [(18)F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated glucose hypermetabolism of the HH, which resolved after cessation of the spasms with adrenocorticotropin hormone treatment. No concurrent increased metabolic activity in the lenticular nuclei or brainstem was observed in the ictal or interictal states. The present case suggests that HHs may be involved in the pathogenesis of infantile spasms, possibly with propagation of epileptic discharges from the hamartoma to the descending spinal pathway.

Ictal movement disorders and hypothalamic hamartoma.

We report the case of a woman presenting with unusual, symptomatic epilepsy related to a hypothalamic hamartoma, in the absence of mental retardation or precocious puberty. The seizures manifested themselves clinically as characteristic, paroxysmal movement disorders, such as choreic/ballistic movement. This type of phenomenon is rarely of epileptic origin: we thus suggest that the movement disorder observed here could be due to functional disorganization of the basal ganglia network by the epileptic discharge, causing loss of the inhibition of thalamic activity and thus allowing the occurrence of abnormal movements.

Differential diagnosis of suprasellar tumors in children.

In contrary to the adult age the most common suprasellar tumors in children are with decreasing frequency craniopharyngiomas, chiasmatic/hypothalamic low-grade gliomas, germinomas and lesions attributable to a Langerhans cell histiocytosis. For differential diagnostic purposes also the rare hypothalamic hamartoma and meningeal metastases in the infundibular recess of the third ventricle are included. The typical aspects of the various tumors on computed tomography (CT) and magnetic resonance imaging (MRI) together with important clinical differences are illustrated. On the basis of imaging results and clinical symptoms differential diagnosis between the various tumor entities should be feasible in many cases. Of course, only in strictly defined cases like typical chiasmatic/hypothalamic and optic pathway gliomas or bilocular germ cell tumors a histological confirmation is dispensable.

Positron emission tomography in epileptogenic hypothalamic hamartomas.

Whether the intrinsic epileptogenicity of hypothalamic hamartomas (HH) is responsible for the entire clinical spectrum of epileptic, neuropsychological and behavioural disorders associated with HH, remains an open issue, in as much as morphologically similar HH can be associated with dramatically different seizure types and cognitive outcomes. The aim of this study was to investigate brain glucose metabolism in patients with epileptogenic HH, in an attempt to identify signs of focal cortical and subcortical dysfunction which might correlate with other clinical data. We have studied five patients with epileptogenic HH using [18F]-fluoro-desoxyglucose and positron emission tomography (FDG-PET). All our patients also underwent an optimal MRI and a video-EEG monitoring, as well as an intra-cranial EEG recording in one of them. The anatomical distribution of FDG-PET abnormalities was compared to that of interictal and ictal electroclinical findings. All five patients demonstrated focal hypometabolism, ipsilateral to the predominant EEG abnormalities and side of HH. Hypometabolic areas greatly varied between patients, but were grossly concordant with the cortical regions suspected to participate in the ictal discharges in each individual. Epileptogenic hypothalamic hamartomas are usually associated with focal cortical hypometabolism in regions which might participate in the overall HH-driven epileptic network. Whether these cortical abnormalities only reflect the propagation of ictal discharges, or a potentially independent seizure onset zone remains unknown.

Utility of early single photon emission computed tomography (SPECT) in neonatal gelastic epilepsy associated with hypothalamic hamartoma.

Gelastic epilepsy, or laughing seizures, is a rare seizure manifestation often associated with hypothalamic hamartoma. This seizure type is well described in older children and adults, but has only rarely been reported in neonates, oftentimes recognized in retrospect when the children are older. We report a child diagnosed at 3 months of age with a large hypothalamic mass after evaluation for spells occurring since birth. The spells were characterized by bursts of hyperpnea, followed by repeated "cooing" respirations, giggling, and smiling. These spells were recognized soon after birth in the delivery room, and occurred at 15-20 minute intervals. They did not interrupt feeding and occurred during sleep. On referral to our center, the patient was noted to be thriving, with normal medical and neurologic examinations except for his spells. The laboratory evaluation was normal, as were endocrine and ophthalmologic evaluations. Neuroimaging was performed, with magnetic resonance imaging demonstrating a large 2.8-cm isodense, nonenhancing hypothalamic mass. Electroencephalogram was abnormal, demonstrating bi-frontal sharp and spike-wave discharges. Video-EEG did not demonstrate ictal discharges associated with the patient's spells. Single photon emission computed tomography (SPECT) demonstrated dramatic ictal uptake in the area of the tumor, with normalization during the interictal phase. Partial excision of hamartomatous tissue has minimally improved the spells. In conclusion, this patient manifested an unusual, early presentation of a rare seizure type. SPECT scanning confirmed the intrinsic epileptogenesis of the hamartoma, further justifying a surgical approach to such patients. Early surgical intervention is probably indicated in an attempt to minimize or prevent the cognitive and behavioral sequelae commonly seen with this seizure type.

Hypothalamic hamartomas and gelastic epilepsy: a spectroscopic study.

BACKGROUND: Patients with hypothalamic hamartomas present with epileptic attacks of laughter and later experience multiple seizure types and cognitive decline, suggestive of secondary generalized epilepsy. It has been suggested in the past that gelastic seizures originate in the temporal lobes rather than in the hamartoma, but temporal resections have been ineffective. Recent electrophysiologic evidence suggests that the epileptogenic discharges may originate in the hamartoma itself. METHODS: We used proton magnetic resonance spectroscopic imaging to quantify the amount of neuronal damage in the temporal lobes and hamartomas of patients with hypothalamic hamartomas and gelastic seizures. Five patients were studied and the relative intensity of N-acetylaspartate to creatine (NAA/Cr) was determined for both temporal lobes as well as for the hamartoma. These values were compared with signals from the temporal lobes and hypothalami of normal control subjects. RESULTS: NAA/Cr was not significantly different from normal control subjects for either temporal lobe, nor was there a significant asymmetry between the two temporal lobes for any of the patients. NAA resonance signals were present in the hamartomas, and the ratio of NAA to Cr was decreased in the hamartomas compared with the hypothalami of normal control subjects (t = 4.5, p = 0.005). CONCLUSIONS: We found no detectable neuronal damage in the temporal lobes of patients with hypothalamic hamartomas and gelastic epilepsy. This is further evidence that gelastic seizures do not originate in the temporal lobes of these patients.

Hypothalamic and pituitary pathology.

This article details the intricate anatomy and elegant physiology of the hypothalamic-pituitary axis. The discussion is meant to confer an understanding of the principles of neuroendocrinology appropriate for the radiologist interpreting imaging studies of this region. The clinical presentations of the diseases that occur in this area of the central nervous system are unique and therefore are discussed in some detail. The radiologic features of the diseases affecting the hypothalamic-pituitary axis are described and correlated with the relevant pathology.