Reversible cerebral vasoconstrictive syndrome preceded by minor head trauma.

Reversible cerebral vasoconstriction syndrome is a heterogeneous and under-recognised neurovascular disorder. Our knowledge with regards to specific syndrome triggers and optimal management is limited. The delay in diagnosis can be deleterious to the patient due to intracerebral sequelae causing temporary or permanent morbidity. Prompt identification of this syndrome is vital to reverse neurological deficits while appropriately managing and supporting patient recovery.

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

OBJECTIVE: The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. DESIGN: One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. RESULTS: Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. CONCLUSION: Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients.

Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

BACKGROUND: Cushing's disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing's syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing's disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia. CASE PRESENTATION: The case is that of a 13-year old boy, presenting with a long history of symptoms and signs suggestive of hypercortisolism, who was found to have cyclical ACTH-dependent hypercortisolism following dynamic pituitary testing and serial late-night salivary cortisol measurements. The patient underwent endoscopic transsphenoidal resection of the pituitary. Early surgical remission was confirmed by undetectable post-operative morning plasma cortisol levels. Histology and immunocytochemistry of the resected pituitary tissue showed extensive corticotroph cell hyperplasia. CONCLUSION: This report describes a rare case of cyclical Cushing's disease secondary to corticotroph hyperplasia in a paediatric patient. This highlights the challenging and varied nature of Cushing's disease and its diagnosis, and the need to keep a differential diagnosis in mind during the diagnostic process.

Presentation, management and outcomes in acute pituitary apoplexy: a large single-centre experience from the United Kingdom.

OBJECTIVE: To study the presentation, management and outcomes and to apply retrospectively the Pituitary Apoplexy Score (PAS) (United Kingdom (UK) guidelines for management of apoplexy) to a large, single-centre series of patients with acute pituitary apoplexy. DESIGN: Retrospective analysis of casenotes at a single neurosurgical centre in Liverpool, UK. RESULTS: Fifty-five patients [mean age, 52·4 years; median duration of follow-up, 7 years] were identified; 45 of 55 (81%) had nonfunctioning adenomas, four acromegaly and six prolactinomas. Commonest presenting features were acute headache (87%), diplopia (47·2%) and visual field (VF) defects (36%). The most frequent ocular palsy involved the 3rd nerve (81%), followed by 6th nerve (34·6%) and multiple palsies (19%). Twenty-three patients were treated conservatively, and the rest had surgery either within 7 days of presentation or delayed elective surgery. Indications for surgery were deteriorating visual acuity and persistent field defects. Patients presenting with VF defects (n = 20) were more likely to undergo surgery (75%) than to be managed expectantly (25%). There was no difference in the rates of complete/near-complete resolution of VF deficits and cranial nerve palsies between those treated conservatively and those who underwent surgery. Endocrine outcomes were also similar. We were able to calculate the PAS for 46 patients: for the group treated with early surgery mean, PAS was 3·8 and for those managed conservatively or with delayed surgery was 1·8. CONCLUSIONS: Patients without VF deficits or whose visual deficits are stable or improving can be managed expectantly without negative impact on outcomes. Clinical severity based on a PAS ≥ 4 appeared to influence management towards emergency surgical intervention.

Is stereotactic radiosurgery under-utilised in the treatment of surgically excisable cerebral metastases?

BACKGROUND/OBJECTIVE: Brain metastases are a significant cause of morbidity and mortality. Treatment options included surgery, whole brain radiotherapy and stereotactic radiosurgery alone or in combination. There has been a significant increase in stereotactic radiosurgery (SRS) provision in the UK over the last 5 years. We investigated the proportion of surgically resected brain metastases that would be suitable for SRS. METHODS: We retrospectively collected data on 116 consecutive patients undergoing surgical resection of brain metastases. Suitable radiological targets for SRS were defined as solid tumours < 30 mm maximum diameter with no hydrocephalus and no symptomatic mass effect. RESULTS: One hundred and two cases (88%) were solitary metastasis and fourteen (12%) had multiple metastases. Median maximum tumour diameter was 34 mm (range: 12-70 mm). Approximately one-third of patients (n = 41) had surgically resected brain metastasis suitable for SRS. Median OS was 7.7 months for those suitable for SRS and 5.4 months for those not suitable for SRS (Fig. 3; Log Rank: P = 0.52). CONCLUSIONS: In surgically amenable tumours, day case SRS could also be used in approximately one-third of cases, thereby avoiding craniotomy and reducing length of stay. These data may be useful in planning service provision, and for drawing up business plans for a new SRS services. Nationally agreed guidelines for SRS for brain metastases have been developed and a full health economic analysis warrants further investigation to determine the cost effectiveness of SRS compared to craniotomy.

A clone of elusive parents: gonadotroph adenoma-female type.

A 69-year-old woman presented with visual disturbance. Perimetry testing revealed a bitemporal hemianopia. Brain MRI demonstrated a 2.2-cm gadolinium-enhancing pituitary mass. Previously she had been treated for hypothyroidism, hypertension, and dyslipidemia. She had hyperprolactinemia. Endoscopic transsphenoidal debulking improved her visual field defects. Histology showed a chromophobic adenoma. Electron microscopy showed elongated, polar cells with long, slender processes. The small uniform secretory granules were peripherally disposed, collecting heavily within cell processes. Based on electron microscopical characteristics the tumor is consistent with an ACTH-negative female gonadotroph adenoma. The parent cell of this rare variant of a pituitary adenoma is yet unknown.

Hypopituitarism--a late consequence of aneurysmal subarachnoid haemorrhage?

Over the last decade subarachnoid haemorrhage (SAH) has increasingly been recognised as a cause of hypopituitarism. We report on the case of a patient with evidence of growth hormone deficiency manifesting after a period of time, with a favourable response to growth hormone replacement. This is followed by a review of the current literature.

The role of a virtual telephone clinic in the follow-up management of lateral skull base tumours.

OBJECTIVE: The purpose of this article was to determine the impact of employing a telephone clinic for follow-up of patients with stable lateral skull-base tumours. METHOD: An analysis of 1515 patients in the national lateral skull-base service was performed, and 148 patients enrolled in the telephone clinic to date were identified. The length of time that patients waited for results of their follow-up scans and the travel distance saved by patients not having to attend the hospital for their results was determined. RESULTS: The mean time from scan to receiving results was 30.5 ± 32 days, 14 days sooner than in the face-to-face group (p = 0.0016). The average round-trip distance travelled by patients to the hospital for results of their scans was 256 ± 131 km. CONCLUSION: The telephone clinic led to a significant reduction in time until patients received their scan results and helped reduce travel distance and clinic numbers in traditional face-to-face clinics.

Dysphagia and hoarse voice: an unusual cause.

We report an unusual presentation and successful treatment of an extracranial skull base carotid aneurysm. The patient presented with a combination of multiple cranial nerve dysfunction and local mass effect. After endovascular treatment of this rare condition her symptoms resolved. The radiological images submitted demonstrate this rare condition well.

Pituitary tuberculoma: a rare cause of sellar mass.

INTRODUCTION: Pituitary tuberculosis is an uncommon cause of sellar mass [1]; the estimated prevalence worldwide is not known, and there have been no reports of the condition occurring in Ireland. Tuberculosis of the pituitary gland may present as a sellar mass or with symptoms of hypopituitarism. CASE PRESENTATION: A 41-year-old woman, with a short prodromal history without endocrine symptoms, was found to have pituitary tuberculosis after the demonstration of a sellar mass on MRI, and lumbar puncture findings consistent with lymphocytic meningitis. CONCLUSION: To our knowledge, this is the first published case of pituitary tuberculoma in Ireland.

Studies of in vitro gamma-interferon production in coeliac disease as a response to gliadin peptides.

The effects of certain fractions of a peptic-tryptic-pancreatinic (PTP) digest of wheat gliadin and of synthetic peptides on the production of gamma interferon (gamma-IFN) in cultures of whole blood from adult patients with coeliac disease (CD) have been studied using a sandwich enzyme immunoassay. The most active peptides were fraction 9, its two principal sub-fractions (sub-fractions 1 and 2) and a synthetic peptide of sequence RPQQPYPQPQPQ (peptide V) corresponding to the principal peptide obtained from reversed-phase HPLC of fraction 9. Results with blood from the control group of subjects also indicated some response to these antigens, in most cases at similar levels to those observed with the coeliacs. Fraction 1 of the PTP digest and the other nine synthetic peptides tested were inactive with both coeliacs and controls. These results are in agreement with the results of in vivo and in vitro toxicity tests. They provide evidence of a link between toxicity and cell-mediated immune response in CD, and suggest that peptide V represents one of the active parts of the gliadin molecule.

De novo antimicrobial peptides with low mammalian cell toxicity.

De novo antimicrobial peptides with the sequences: (KLAKKLA)n, (KLAKLAK)n (where n = 1,2,3), (KALKALK)3, (KLGKKLG)n, and (KAAKKAA)n (where n = 2,3), were prepared as the C-terminus amides. These peptides were designed to be perfectly amphipathic in helical conformations. Peptide antibacterial activity was tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Peptide cytotoxicity was tested against human erythrocytes and 3T3 mouse fibroblasts. The 3T3 cell testing was a much more sensitive test of cytotoxicity. The peptides were much less lytic toward human erythrocytes than 3T3 cells. Peptide secondary structure in aqueous solution, sodium dodecylsulfate micelles, and phospholipid vesicles was estimated using circular dichroism spectroscopy. The leucine/alanine-containing 21-mers were bacteriostatic at 3-8 microM and cytotoxic to 3T3 cells at about 10 microM concentrations. The leucine/alanine- or leucine/glycine-containing 14-mers and the leucine/glycine 21-mer were bacteriostatic at 6-22 microM but had much lower cytotoxicity toward 3T3 cells and higher selectivities than the natural antimicrobial peptides magainin 2 amide and cecropin B amide. The 7-mer peptides are devoid of biological activity and of secondary structure in membrane mimetic environments. The 14-mer peptides and the glycine-containing 21-mer show modest levels of helicity in model membranes. The leucine/alanine-containing 21-mer peptides have substantial helicity in model membranes. The propensity to alpha-helical conformation of the peptides in amphipathic media is proportional to their 3T3 cell cytotoxicity.

Craniovertebral abnormalities in Type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome).

INTRODUCTION: The craniovertebral abnormalities found in patients with Type VI mucopolysaccharidosis (Maroteaux-Lamy syndrome) are described, and the indications for and outcomes of surgery in this group are assessed. METHODS: The clinical histories and radiological findings in all patients with Type VI mucopolysaccharidosis treated at Royal Manchester Children's Hospital during the past 10 years were reviewed. RESULTS: The typical findings in patients with this disease are of canal stenosis at the level of the foramen magnum and upper cervical spine with or without cord compression. The stenosis is secondary to thickening of the posterior longitudinal ligament. Atlantoaxial instability is rare. Of nine patients under regular clinical review, four underwent decompressive surgery for cervical cord compression. Three of the four showed improvement in their neurological symptoms and signs postoperatively. Of the children reviewed, six had radiological evidence of cord compression, although only those with neurological signs or symptoms were treated surgically. DISCUSSION: Despite the often formidable anesthetic challenge, surgery is indicated in those patients who present with progressive neurological deficit due to cervical myelopathy. Surgery can be undertaken safely if the associated medical problems in these children are recognized and managed appropriately.

Solitary exostosis of the thoracic spine. Early diagnosis and treatment.

STUDY DESIGN: A case report. OBJECTIVE: To highlight the importance of early diagnosis and treatment of vertebral exostosis. SUMMARY OF BACKGROUND DATA: Few cases of spinal cord compression caused by solitary thoracic exostoses have been reported. METHOD: A solitary exostosis in the midline of the neural arch of the fifth thoracic vertebra, causing compression of the spinal cord documented on both magnetic resonance and computed tomographic examinations, is reported in a 51-year-old woman who had normal findings in a neurologic examination. RESULTS: The exostosis was successfully excised. CONCLUSION: Accurate preoperative diagnosis of vertebral exostoses is possible using magnetic resonance and computed tomography. Early excision avoids the development of a permanent neurologic deficit.

Conservative management of vestibular schwannomas of 15 to 31 mm intracranial diameter.

OBJECTIVE: To study the natural course of vestibular schwannomas 15 to 31 mm in diameter. METHODS: A retrospective study of 45 patients conservatively managed with interval scanning was performed. Outcome measures were: changes in tumour size, clinical features and hearing. A tumour was considered to be growing if it increased in size by more than 2 mm. RESULTS: Initial tumour sizes ranged from 15 to 31 mm, with a mean (± standard deviation) diameter of 20.1 ± 4.3 mm. The duration of follow up ranged from 6 months to 14 years (median, 3 years). Tumours grew in 11 cases (24.4 per cent), remained stable in 30 cases (66.7 per cent) and regressed in 4 cases (8.9 per cent). The overall mean tumour growth rate was 0.9 ± 2.2 mm per year; in growing tumours, it was 3.6 ± 2.9 mm per year. CONCLUSION: Outcomes were similar to those reported for smaller tumours. These findings suggest that patients with medium or moderately large tumours can be safely offered an initial period of conservative management before intervention is considered.

Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting.

CONTEXT: Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE: The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN: This was a prospective cohort study. SETTING: The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS: One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS: Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES: Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS: Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS: The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.

The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency.

BACKGROUND: Adult GHD syndrome is associated with clustering of adverse cardiovascular (CV) risk factors such as abnormal body composition, dyslipidemia, insulin resistance and abnormal haemostatic factors. There is a wealth of evidence linking CV events with elevated levels of inflammatory markers (hs-CRP and IL-6) in the general population; however data on their abnormalities in GHD and specially the effects of GH replacement (GHR) on these inflammatory markers are limited. OBJECTIVE: To study the effects of GHR on inflammatory markers, glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease. DESIGN: Fifteen hypopituitary adults (11 males, mean age 48.5 years) with recently diagnosed, severe GHD were recruited. Patients received GHR (in addition to other pituitary hormone replacements) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels. Weight, waist hip ratio (WHR), body composition, fasting plasma glucose and insulin, insulin resistance index (HOMA-IR), fasting serum lipid levels, hs-CRP, IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR. RESULTS: GHR resulted in a physiological increase in IGF-1 SDS [median -0.6 to +0.39, P<0.0001], improved quality of life (mean pre-treatment AGHDA score 16 vs. post-treatment score 7, P<0.0001) and reduction in WHR (0.94 vs. 0.92, P=0.01). There were no significant changes in body weight and composition. Levels of hs-CRP (log transformed, mean (SD)) were significantly reduced following GHR (pre 1.21 (0.9) vs. post 0.27 (0.9), P<0.0001) but TNF-alpha and IL-6 levels remained unchanged. Fasting glucose (mmol/L) [4.6 (0.1) vs. 5.1 (0.1), P=0.003], fasting insulin (muU/mL) [9.4 (8.1) vs. 12.1 (9.2), P=0.03] and HOMA-IR [1.2 (1.0) vs. 1.5 (1.1) P=0.02] (all pre-GHR vs. post-GHR and mean (SD)) significantly increased following GHR indicating increased insulin resistance. Significant improvements were noted in fasting LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels following GHR [3.4 (0.9) vs. 2.9 (0.7), P=0.03 and 1.2 (0.2) vs. 1.3 (0.2), P=0.02, respectively] (all pre-GHR vs. post-GHR and mean (SD)). Levels of total cholesterol and triglycerides did not change following GHR. CONCLUSIONS: Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD resulted in favourable changes in hs-CRP, WHR, fasting LDL-C and HDL-C levels all of which are recognised CV risk markers. However, there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR, monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population.