Swallowing Assessment in Parkinson's Disease: Patient and Investigator Reported Outcome Measures are not Aligned.

This study determines the relationship between patient and investigator reported outcome measures (PROMs versus IROMs) on oropharyngeal dysphagia (OD) in Parkinson's disease (PD). The PROMs used are the MD Anderson Dysphagia Inventory (MDADI) and the Dysphagia Severity Scale (DSS). The IROMs used are fiberoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy of swallowing (VFS). Ninety dysphagic PD patients were included. Multilayer perceptron (MLP) neural network analysis was used to investigate the relationship between PROMs and IROMs on OD in PD. MLP neural network analysis showed a moderate agreement between PROMs and IROMs, with an area under the curve between 0.6 and 0.7. Two-step cluster analysis revealed several clusters of patients with similar scores on FEES and/or VFS variables, but with significant different scores on MDADI and DSS variables. This study highlights that there are PD patients with similar FEES and/or VFS findings that cannot be lumped together under the same pathophysiological umbrella due to their differences in PROMs. Since the exact origin of these differences is not fully understood, it seems appropriate for the time being to take into account the different dimensions of OD during the swallowing assessment so that they can be included in a patient-tailored treatment plan.

Feasibility of electronic nose technology for discriminating between head and neck, bladder, and colon carcinomas.

Electronic nose (e-nose) technology has the potential to detect cancer at an early stage and can differentiate between cancer origins. Our objective was to compare patients who had head and neck squamous cell carcinoma (HNSCC) with patients who had colon or bladder cancer to determine the distinctive diagnostic characteristics of the e-nose. Feasibility study An e-nose device was used to collect samples of exhaled breath from patients who had HNSCC and those who had bladder or colon cancer, after which the samples were analyzed and compared. One hundred patients with HNSCC, 40 patients with bladder cancer, and 28 patients with colon cancer exhaled through an e-nose for 5 min. An artificial neural network was used for the analysis, and double cross-validation to validate the model. In differentiating HNSCC from colon cancer, a diagnostic accuracy of 81 % was found. When comparing HNSCC with bladder cancer, the diagnostic accuracy was 84 %. A diagnostic accuracy of 84 % was found between bladder cancer and colon cancer. The e-nose technique using double cross-validation is able to discriminate between HNSCC and colon cancer and between HNSCC and bladder cancer. Furthermore, the e-nose technique can distinguish colon cancer from bladder cancer.

[Delayed diagnosis of Huntington's disease in a psychiatric setting]. / Vertraagde diagnose van de ziekte van Huntington in een psychiatrische setting.

Huntington's disease (hd) is characterised by a triad of neuropsychiatric symptoms, motor disturbances and cognitive decline. If initial symptoms are of neuropsychiatric nature they maybe misinterpreted, which can lead to delayed diagnosis. Three examples of delayed hd diagnosis in a psychiatric setting are discussed.

Different prognostic models for different patient populations: validation of a new prognostic model for patients with oropharyngeal cancer in Western Europe.

OBJECTIVE: The presence of human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant in prognostic risk modelling. Recently, a prognostic model was proposed in which HPV status, comorbidity and nodal stage were the most important prognostic factors to determine high-, intermediate- and low-risk survival groups. Here, we report on the validation of this model using an independent single-institutional cohort. METHODS: A total number of 235 patients curatively treated for OPSCC in the period 2000-2011 at the MUMC (Maastricht University Medical Center, The Netherlands) were included. The presence of an oncogenic HPV infection was determined by p16 immunostaining, followed by a high-risk HPV DNA PCR on the p16-positive cases. The model variables included were HPV status, comorbidity and nodal stage. As a measure of model performance, the Harrell's Concordance index (Harrell's C-index) was used. RESULTS: The 5-year overall survival (OS) estimates were 84.6%, 54.5% and 28.7% in the low-, intermediate- and high-risk group, respectively. The difference between the survival curves was highly significant (P<0.001). The Harrell's C-index was 0.69 (95% confidence interval (CI): 0.63-0.75). CONCLUSION: In this study a previously developed prognostic risk model was validated. This model will help to personalise treatment in OPSCC patients. This model is publicly available at www.predictcancer.org.

Blood-brain barrier disruption during spontaneous canine visceral leishmaniasis.

Visceral leishmaniasis is a complex disease caused by Leishmania infantum, and in dogs, besides the classical symptoms, there are descriptions of inflammatory alterations in the brain. Brain inflammation is a strictly controlled process, and as the brain counts on the efficiency of the blood-brain barrier (BBB), we aimed to assess BBB integrity in dogs with spontaneous visceral leishmaniasis. Therefore, we evaluated markers in the cerebrospinal fluid (CSF) and in brain tissue related to BBB disruption and brain inflammation. Elevated albumin quota revealed BBB breakdown, corroborated by increased concentrations of anti-Leishmania antibodies in the CSF. In the brain, albumin and IgG staining formed halos around blood vessels, a classical indicator of BBB leakage. Soluble IgG was also detected in the choroid plexus and ependyma, and in these structures, IgG stained random resident cells. IgG(+) cells and Fcγ-RI(+) cells were identified in the choroid plexus, ependyma and perivascular in the brain parenchyma. The data support the occurrence of BBB disruption in dogs with spontaneous visceral leishmaniasis, and IgG as a key molecule that is capable of initiating and/or maintaining the inflammatory stimuli in the nervous milieu and the CSF as an important disseminator of inflammatory stimuli within the CNS.

Allergic rhinitis is a risk factor for traffic safety.

BACKGROUND: Allergic rhinitis (AR) affects up to 30% of the adult population and symptomatic patients continue to engage in daily life activities, including car driving. Previous studies have shown that AR can impair cognitive functions, especially during longer-lasting tasks. Other reports suggest negative effects on psychomotor functions such as driving, but no clear evidence has been presented yet. OBJECTIVES: Primary objective was to determine the effect of AR per se on actual driving performance and compare it with the effects of treated AR. METHODS: Nineteen patients with documented AR history underwent a unique and validated 1-h on-the-road driving test outside the pollen season. In a 4-leg repeated measures design, patients underwent a nasal provocation test with either pollen or inactive control prior to the driving test. In the three conditions with pollen provocation, patients were pretreated with either cetirizine 10 mg, fluticasone furoate 27.5 µg, or placebo to alleviate the provoked AR symptoms. RESULTS: The driving performance of patients when symptomatic and not treated was significantly impaired compared to the placebo condition. When engaging in a secondary memory task during driving, their performance deteriorated further. The magnitude of impairment was relevant and comparable to that seen at a blood alcohol level of 0.05%, the legal limit in many countries. Treatment of AR symptoms partially counteracted the effect of AR on driving. CONCLUSIONS: Untreated AR can impair driving ability and put patients at risk. Drug therapy reduces this impairment, and AR patients should therefore be advised to always treat their condition.

[Embrace, a model for integrated elderly care]. / SamenOud, een model voor geïntegreerde ouderenzorg: studieprotocol van een gerandomiseerde studie naar de effectiviteit betreffende patiëntuitkomsten, kwaliteit van zorg, zorggebruik en kosten.

UNLABELLED: Ongoing growth in health care expenditures and changing patterns in the demand for health care challenge societies worldwide. The Chronic Care Model (CCM), combined with classification for care needs based on Kaiser Permanente (KP) Triangle, may offer a suitable framework for change. The aim of the present study is to investigate the effectiveness of Embrace, a population-based model for integrated elderly care, regarding patient outcomes, service use, costs, and quality of care. METHODS: The CCM and the KP Triangle were translated to the Dutch setting and adapted to the full elderly population living in the community. A randomized controlled trial with balanced allocation was designed to test the effectiveness of Embrace. Eligible elderly persons are 75 years and older and enrolled with one of the participating general practitioner practices. Based on scores on the INTERMED-Elderly Self-Assessment and Groningen Frailty Indicator, participants will be stratified into one of three strata: (A) robust; (B) frail; and (C) complex care needs. Next, participants will be randomized per stratum to Embrace or care as usual. Embrace encompasses an Elderly Care Team per general practitioner practice, an Electronic Elderly Record System, decision support instruments, and a self-management support and prevention program - combined with care and support intensity levels increasing from stratum A to stratum C. Primary outcome variables are patient outcomes, service use, costs, and quality of care. Data will be collected at baseline, twelve months after starting date, and during the intervention period. DISCUSSION: This study could provide evidence for the effectiveness of Embrace.

[Subcutaneous nodules of the head and neck heralding giant cell arteritis]. / Nodules sous-cutanés cervico-céphaliques précédant l'apparition d'une artérite à cellules géantes.

BACKGROUND: Giant cell arteritis is the most common form of systemic vasculitis affecting individuals aged over 50 years. While its clinical manifestations are numerous, cutaneous involvement is uncommon and rarely constitutes the initial sign. We discuss a case of atypical skin involvement as the initial symptom of giant cell arteritis. OBSERVATION: An 86-year-old woman presented purplish and painful subcutaneous nodules on the scalp and neck. Biological explorations showed systemic inflammation. The skin biopsy was evocative of polyarteritis nodosa. The nodules spontaneously disappeared completely, and asthenia and bitemporal headache gradually appeared. In view of the persistent inflammatory syndrome, a diagnosis of giant cell arteritis was proposed and was later confirmed by the temporal artery biopsy sample, with its typical histological appearance. Systemic corticosteroids resulted in complete regression of symptoms within a few days. DISCUSSION: To our knowledge, inflammatory cervical subcutaneous nodules have never been described in giant cell arteritis. The case we report herein thus raises the issue of differential diagnosis between various forms of vasculitis. While classification of the latter continues to progress thanks to improvements in physiopathological knowledge, the distinction between vasculitis of the large and small vessels remains tenuous on occasion. We discuss the differential diagnoses. CONCLUSION: The dermatological presentation of giant cell arteritis in the present case suggests the existence of a continuum between small-, medium- and large-vessel vasculitis.

Definitive radiation therapy for treatment of laryngeal carcinoma: impact of local relapse on outcome and implications for treatment strategies.

PURPOSE: The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures. METHODS AND MATERIALS: In all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival. RESULTS: Median follow-up was 38 months (range 1-144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10%, cT2 18%, cT3 23%, and cT4 36% (p<0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76%). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68% for cT1, cT2, cT3, and cT4 tumors (p<0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26% (p<0.001), respectively. Overall survival at 5 years was 68% for patients without local relapse and 50% for patients experiencing local failure (p<0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3-4 tumors, only tumor volume remained statistically significant (HR 1.017, p=0.001) for local relapse-free survival. CONCLUSION: Local control rates for cT1-2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3-4 tumors treated with RT alone, initial local control rates are moderate, and in 60% of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.

Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.

Huntington's disease (HD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene. We have assessed 360 HD individuals from 259 unrelated families and found a highly significant correlation (r = 0.70, p = 10(-7)) between the age of onset and the repeat length, which accounts for approximately 50% of the variation in the age of onset. Significant associations were also found between repeat length and age of death and onset of other clinical features. Sib pair and parent-child analysis revealed that the CAG repeat demonstrates only mild instability. Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs.

Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects.

Huntington's disease (HD) is associated with expansion of a CAG repeat in a novel gene. We have assessed 21 sporadic cases of HD to investigate sequential events underlying HD. We show the existence of an intermediate allele (IA) in parental alleles of 30-38 CAG repeats in the HD gene which is greater than usually seen in the general population but below the range seen in patients with HD. These IAs are meiotically unstable and in the sporadic cases, expand to the full mutation associated with the phenotype of HD. This expansion has been shown to occur only during transmission through the male germline and is associated with advanced paternal age. These findings suggest that new mutations for HD are more frequent than prior estimates and indicate a previously unrecognized risk of inheriting HD to siblings of sporadic cases of HD and their children.

The effects of surface electrical stimulation plus voice therapy in Parkinson's disease.

OBJECTIVE: This study aimed to assess the effects of surface electrical stimulation plus voice therapy on voice in dysphonic patients with idiopathic Parkinson's disease. METHOD: Patients were assigned to 3 treatment groups (n = 28 per group) and received daily treatment for 3 weeks on 5 days a week. All three groups received voice therapy (usual care). In addition, two groups received surface electrical stimulation, either motor-level or sensory-level stimulation. A standardised measurement protocol to evaluate therapeutic effects included the Voice Handicap Index and videolaryngostroboscopy. RESULTS: Voice Handicap Index and videolaryngostroboscopic assessment showed statistically significant differences between baseline and post-treatment across all groups, without any post-treatment differences between the three groups. CONCLUSION: Intensive voice therapy (usual care) improved idiopathic Parkinson's disease patients' self-assessment of voice impairment and the videolaryngostroboscopic outcome score. However, surface electrical stimulation used as an add-on to usual care did not improve idiopathic Parkinson's disease patients' self-assessment of voice impairment or the videolaryngostroboscopic outcome scores any further.

Autosomal recessive cerebellar ataxias: the current state of affairs.

Among the hereditary ataxias, autosomal recessive cerebellar ataxias (ARCAs) encompass a diverse group of rare neurodegenerative disorders in which a cerebellar syndrome is the key clinical feature. The clinical overlap between the different cerebellar ataxias, the occasional atypical phenotypes, and the genetic heterogeneity often complicate the clinical management of such patients. Despite the steady increase in newly discovered ARCA genes, many patients with a putative ARCA cannot be genotyped yet, proving that more genes must be involved. This review presents an updated overview of the various ARCAs. The clinical and genetic characteristics of those forms with a known molecular genetic defect are discussed, along with the emerging insights in the underlying pathophysiological mechanisms.

Disturbed cognitive functions after nasal provocation in patients with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) reduces quality of life as a result of impaired psychological well-being and perceived impaired cognitive functioning. Few studies have measured cognitive functions objectively and it remains uncertain whether AR leads to an objective reduction in cognitive functions. OBJECTIVE: The present study investigated whether AR is associated with a decrement in several aspects of cognitive functioning. Furthermore, the study investigated whether AR patients invest more 'mental effort' in order to achieve the same cognitive performances as healthy controls. METHODS: Twenty five patients with seasonal allergic rhinitis (SAR) and 26 healthy controls, matched for age, education and sex, were tested on a battery of time-demanding and strenuous objective cognitive tests and subjective questionnaires, both before and after nasal provocation (NP). The cognitive functions assessed were sustained attention, short- and long-term memory and speed of information processing. Mental effort was assessed using visual rating scales. RESULTS: Sustained but not short cognitive performance was impaired in patients after NP. Patients showed an increased effort on short cognitive tests. CONCLUSION: SAR patients suffer from cognitive performance decrements that can be compensated by additional mental effort for short tasks only.

Morphological MRI criteria improve the detection of lymph node metastases in head and neck squamous cell carcinoma: multivariate logistic regression analysis of MRI features of cervical lymph nodes.

The aim was to evaluate whether morphological criteria in addition to the size criterion results in better diagnostic performance of MRI for the detection of cervical lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). Two radiologists evaluated 44 consecutive patients in which lymph node characteristics were assessed with histopathological correlation as gold standard. Assessed criteria were the short axial diameter and morphological criteria such as border irregularity and homogeneity of signal intensity on T2-weighted and contrast-enhanced T1-weighted images. Multivariate logistic regression analysis was performed: diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) and areas under the curve (AUCs) of receiver-operating characteristic (ROC) curves were determined. Border irregularity and heterogeneity of signal intensity on T(2)-weighted images showed significantly increased DORs. AUCs increased from 0.67 (95% CI: 0.61-0.73) using size only to 0.81 (95% CI: 0.75-0.87) using all four criteria for observer 1 and from 0.68 (95% CI: 0.62-0.74) to 0.96 (95% CI: 0.94-0.98) for observer 2 (p < 0.001). This study demonstrated that the morphological criteria border irregularity and heterogeneity of signal intensity on T2-weighted images in addition to size significantly improved the detection of cervical lymph nodes metastases.

Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma.

INTRODUCTION: The aim was to determine the diagnostic accuracy and additional value of diffusion-weighted imaging for detection of malignant lymph nodes in head and neck squamous cell carcinoma. METHODS: Two hundred nineteen lymph nodes, predominantly smaller than 10 mm (95.4%), in 16 consecutive patients were evaluated at 1.5 T. Lymph nodes were evaluated for maximum short axial diameter, morphological criteria, and apparent diffusion coefficient (ADC) values (b = 0 and b = 1,000 s/mm(2)). Sensitivity, specificity, positive and negative predictive values as well as diagnostic odds ratios (DORs) and areas under the curves (AUCs) of ROC curves were calculated for the various magnetic resonance imaging (MRI) criteria individually and in combination. Histological examination of lymph nodes in the neck dissection specimen was the gold standard to determine malignant involvement. RESULTS: The optimal ADC threshold was 1.0 x 10(-3) mm(2)/s. Using this cutoff point, sensitivity and specificity were 92.3% and 83.9%, respectively. When used in combination with size and morphological criteria, ADC value <1.0 x 10(-3) mm(2)/s was the strongest predictor of presence of metastasis (DOR = 97.6). A model which added ADC values to the other MRI criteria performed significantly better than a model without ADC values: AUC = 0.98 versus AUC = 0.91 (p = 0.036). CONCLUSION: In this study, with predominantly small lymph nodes, the ADC criterion is the strongest independent predictor of presence of metastasis. The use of ADC values in combination with the other MRI criteria significantly improves the discrimination between malignant and benign lymph nodes.

"Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia.

BACKGROUND AND PURPOSE: The "ears of the lynx" MR imaging sign has been described in case reports of hereditary spastic paraplegia with a thin corpus callosum, mostly associated with mutations in the spatacsin vesicle trafficking associated gene, causing Spastic Paraplegia type 11 (SPG11). This sign corresponds to long T1 and T2 values in the forceps minor of the corpus callosum, which appears hyperintense on FLAIR and hypointense on T1-weighted images. Our purpose was to determine the sensitivity and specificity of the ears of the lynx MR imaging sign for genetic cases compared with common potential mimics. MATERIALS AND METHODS: Four independent raters, blinded to the diagnosis, determined whether the ears of the lynx sign was present in each of a set of 204 single anonymized FLAIR and T1-weighted MR images from 34 patients with causal mutations associated with SPG11 or Spastic Paraplegia type 15 (SPG15). 34 healthy controls, and 34 patients with multiple sclerosis. RESULTS: The interrater reliability for FLAIR images was substantial (Cohen κ, 0.66-0.77). For these images, the sensitivity of the ears of the lynx sign across raters ranged from 78.8 to 97.0 and the specificity ranged from 90.9 to 100. The accuracy of the sign, measured by area under the receiver operating characteristic curve, ranged from very good (87.1) to excellent (93.9). CONCLUSIONS: The ears of the lynx sign on FLAIR MR imaging is highly specific for the most common genetic subtypes of hereditary spastic paraplegia with a thin corpus callosum. When this sign is present, there is a high likelihood of a genetic mutation, particularly associated with SPG11 or SPG15, even in the absence of a family history.

SPG10 is a rare cause of spastic paraplegia in European families.

BACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. OBJECTIVE: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype. PATIENTS AND METHODS: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families. RESULTS: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory-motor neuropathy was detected by neurophysiology studies. CONCLUSIONS: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy.

Serious post-tonsillectomy hemorrhage with and without lethal outcome in children and adolescents.

BACKGROUND: Serious post-tonsillectomy hemorrhage (PTH) is an uncommon complication requiring immediate and adequate medical treatment. This study was undertaken to describe and evaluate the clinical data and courses of serious PTH, with and without lethal outcome in children and adolescents. MATERIALS AND METHODS: Bleeding episodes accompanied by hemorrhagic shock requiring resuscitation and/or major medical treatment were labeled as serious PTH, with or without lethal outcome. Personal experiences as surgeons and expert reports in connection with lawsuits and Professional Boards, as well as reports collected after a published request contributed to the data collection. RESULTS: Thirty-one boys and 21 girls (gender not stated for three patients) younger than 18 years of age were enrolled in our study (mean: 8.47; median: 6; S.D.: 4.73 years). Thirty-three children were 8 years of age or younger (60%). Lethal outcome was reported for 19 patients of whom 11 had experienced repeated episodes of bleeding. The majority of the surviving children experienced serious PTH without remaining sequelae (32), however, four children suffered from remaining sequelae. Forty-three children experienced repeated episodes of PTH. The first episode of PTH occurred either at home (32) or in the hospital (22; location not stated for one child). Primary hemorrhage (<24h) was reported for three, secondary bleeding (>24h) for 52 children (94.5%). A total of 169 bleeding episodes was reported of whom 149 were specified as massive (56), major (31), minor (15), diffuse (12), with spontaneous cessation (19) or vomiting of considerable amounts of blood (16). Aspiration was confirmed at the autopsy of seven patients. Ligature of greater arteries in the neck was performed in 35 cases, suturing of the faucal pillars in four and packing of the oropharynx in six patients. Twenty-four children received blood transfusions. Resuscitation was performed in 17 cases but remained ineffective in seven patients. CONCLUSION: Repeated episodes of bleeding should be considered as a warning sign of serious PTH. Inpatient observation does not eliminate the risk of lethal outcome. Children up to 8 years of age seem to be more susceptible to serious PTH, whereas gender remained irrelevant as a contributing risk factor. Life-threatening PTH is likely to occur as secondary PTH.