Farhad Afshar

Stereotactic localization of the human pedunculopontine nucleus: atlas-based coordinates and validation of a magnetic resonance imaging protocol for direct localization

The pedunculopontine nucleus (PPN) is a promising new target for deep brain stimulation (DBS) in parkinsonian patients with gait disturbance and postural instability refractory to other treatment modalities. This region of the brain is unfamiliar territory to most functional neurosurgeons. This paper reviews the anatomy of the human PPN and describes novel, clinically relevant methods for the atlas-based and MRI-based localization of the nucleus. These two methods of PPN localization are evaluated and compared on stereotactic MRI data acquired from a diverse group of 12 patients undergoing implantation of deep brain electrodes at sites other than the PPN. Atlas-based coordinates of the rostral and caudal PPN poles in relation to fourth ventricular landmarks were established by amalgamating information sourced from two published human brain atlases. These landmarks were identified on acquired T1 images and atlas-derived coordinates used to plot the predicted PPN location on all 24 sides. Images acquired using a specifically modified, proton-density MRI protocol were available for each patient and were spatially fused to the T1 images. This widely available and rapid protocol provided excellent definition between gray and white matter within the region of interest. Together with an understanding of the regional anatomy, direct localization of the PPN was possible on all 24 sides. The coordinates for each directly localized nucleus were measured in relation to third and fourth ventricular landmarks. The mean (SD) of the directly localized PPN midpoints was 6.4 mm (0.5) lateral, 3.5 mm (1.0) posterior and 11.4 mm (1.2) caudal to the posterior commissure in the anterior commissure-posterior commissure plane. For the directly localized nucleus, there was similar concordance for the rostral pole of the PPN in relation to third and fourth ventricular landmarks (P>0.05). For the caudal PPN pole, fourth ventricular landmarks provided greater concordance with reference to the anteroposterior coordinate (P<0.001). There was a significant difference between localization of the PPN poles as predicted by atlas-based coordinates and direct MRI localization. This difference affected mainly the rostrocaudal coordinates; the mean lateral and anteroposterior coordinates of the directly localized PPN poles were within 0.5 mm of the atlas-based predicted values. Our findings provide simple, rapid and precise methods that are of clinical relevance to the atlas-based and direct stereotactic localization of the human PPN. Direct MRI localization may allow greater individual accuracy than that afforded by atlas-based coordinates when localizing the human PPN and may be relevant to groups evaluating the clinical role of PPN DBS.

Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing's syndrome

OBJECTIVE Cushings syndrome In childhood and adolescence Is rare. We analysed the clinical presentation, Investigation, management and therapeutic outcome In 12 paediatric patients with Cushings syndrome.

Cushing’s Disease in Childhood: Presentation, Investigation, Treatment and Long-Term Outcome

Seventeen patients with Cushing’s disease (CD) were treated from 1978 to 2000. There were 11 males and 6 females aged 6.8–18.8 years (mean age 13.0 ± 5.9 years). Presenting features were: weight gain (100%); growth failure (71%); hirsutism (53%); striae (53%); hypertension (47%). Mean age of patients with striae was 15.2 ± 2.3 years, without striae 10.3 ± 3.3 years. Median height SDS was –1.81 (range –0.28 to –4.17), 53% having height SDS < –1.8. The height velocity in 6 subjects was subnormal (0.9–3.8 cm/year). Median BMI SDS was 2.29 (range 1.72–5.06). Cushing’s disease was confirmed by detectable serum ACTH, median 28 ng/l (range 12–99, NR <10–50) (n = 15); loss of cortisol circadian rhythm values at midnight ranging from 216 to 1,080 nmol/l (NR <50) (n = 15); lack of cortisol suppression (NV < 50 nmol/l) during low-dose dexamethasone suppression test (LDDST) (0.5 mg 6-hourly × 8) (n = 14); and >50% suppression of cortisol compared with the basal value during high-dose dexamethasone suppression test (HDDST) (2 mg 6-hourly × 8) (n = 14). A CRH test (1 µg/kg i.v.) showed an increase of cortisol from 12 to 217% (median 73.5%) (n = 16). Pituitary imaging (CT/MRI) showed an image consistent with microadenoma in 6/17 patients, but there was concordance between pituitary imaging and surgical findings in 1/11 patients (9%). Inferior petrosal sinus sampling (IPSS) for ACTH after CRH was performed in 11 subjects (age 10.7–18.8 years). Central to peripheral ACTH ratios were >2 (2.5–157.2) in 10/11 patients. The inter-petrosal sinus ACTH gradient was >1.4 in 10 patients (2.1–20.8), indicating lateralization of ACTH secretion. In 10 patients (91%), the side of the tumour on IPSS was predictive of findings at surgery. Therapy consisted of transsphenoidal microadenomectomy (TSS) in 16 patients and bilateral adrenalectomy (1978) in 1. Following TSS alone, 7 patients were cured (cortisol <50 nmol/l) and 2 were in remission (cortisol <300 nmol/l), i.e. 56%. Seven had persisting hypercortisolaemia and underwent pituitary irradiation (4,500 cGy). Therapeutic outcome for a median of 8 years (0.5–24 years) resulted in cure of CD in 14/17 patients (82%) and remission in 1. Linear growth after TSS ± pituitary irradiation in 10 subjects showed no short-term catch-up growth, with peak growth hormone (GH) 0.5–20.9 mU/l to insulin tolerance test (ITT)/glucagon. Eight patients were treated with human growth hormone (hGH) (14 U/m2/week) combined in 3 with GnRH analogue. The mean final (n = 6) or latest (n = 4) height SDS was –1.36. The difference between final/latest height SDS and target height SDS was 0.93 ± 1.13, i.e. less (p = 0.005) than the difference between height SDS and target height SDS at presentation, i.e. 1.72 ± 1.26, indicating long-term catch-up growth.

Schwannoma of the anterior cranial fossa and paranasal sinuses

Only two cases of schwannomas involving the anterior cranial fossa and paranasal sinuses or nasal fossa have been reported previously. We describe a third case which involved all of these structures and also the left orbit.

Bromocriptine-induced cerebrospinal fluid rhinorrhea

Abstract We describe a case of hyperprolactinemia in a patient with sellar enlargement shown radiologically who, after a short course of bromocriptine, developed cerebrospinal fluid (CSF) rhinorrhea. The causal effects and relationship between tumor shrinkage resulting from bromocriptine administration and subsequent CSF rhinorrhea are discussed.

Advances in the Management of Paediatric Cushing’s Disease

Cushing’s disease (CD) is rare in the paediatric age range, but may present a difficult therapeutic challenge. Most paediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. Prior to definitive treatment, a diagnostic protocol for investigation is required which broadly follows the model for adult patients. Treatment strategies for CD are described and critically appraised. The management of paediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life.

Chronic Spontaneous Tension Pneumocephalus Due to Benign Frontal Sinus Osteoma

Spontaneous pneumocephalus secondary to neoplasia is a rare condition. It may present with headaches, rhinorrhoea, otorrhoea, or meningitis in various combinations. A case of unusual presentation, with several months delay in diagnosis, with remarkable postoperative improvement is reported and the literature reviewed.

Transsphenoidal Chiasmopexy for Long Standing Visual Failure in the Secondary Empty Sella Syndrome

The development of an empty sella syndrome is a well recognized complication in the treatment of pituitary tumours and usually presents with visual failure. Transsphenoidal chiasmopexy has been successful in reversing the visual loss when performed in the acute stage. A case, where a delay of 18 months in the surgery does not appear to have affected the outcome, is presented and the literature reviewed.

Giant cell tumour of the sphenoid bone with coincidental galactorrhoea-a case report

A case of the rare giant cell tumour involving the sphenoid bone is reported. The usual presentation of these tumours is headache and cranial nerve deficits. This 25-year-old lady presented with oligomenorrhoea and galactorrhoea. Investigations demonstrated an asymptomatic erosive mass lesion in the sphenoid with suprasellar extension and extension into the nasopharynx. The tumour was partially resected via the transphenoidal route. The differential diagnosis and treatment of these lesions are discussed.

Metastatic Carcinoid Tumour of the CNS from two different primary sites

Two cases of carcinoid tumour affecting the central nervous system through their metastases were treated surgically. The first case was carcinoid tumour of the lung with a single metastases in the right frontal lobe of the brain, while the second developed metastases of the sixth thoracic vertebra from a terminal ileum bowel primary causing spinal cord compression. Neither case developed carcinoid syndrome. The rarity of such metastases affecting the central nervous system is discussed together with a review of the literature.