When rare diseases crisscross within the same patient: von Hippel-Lindau and type 1 gastric neuroendocrine tumor.

Von-Hippel-Lindau (VHL) is a genetic multisystem disorder characterized by visceral cysts and benign and malignant tumors in various organs. Herein, we present the case of a 23-year-old woman with VHL presenting with multiple gastric neuroendocrine neoplasms (gNENs) type 1 in the context of chronic autoimmune gastritis (CAG). Although gNENs are not acknowledged as a typical entity in VHL patients, in the present case, gNENs were composed of neoplastic cells with clear cytoplasm usually seen in tumors related to VHL disease. We additionally performed a literature review on the presence of neuroendocrine clear cell tumors and report on further cases of clear cell NENs. The present case illustrates that clear-cell transformation in gNENs may be due to the dual genetic background of the patient; the real oncogenic stimulus may be more closely related to CAG than to VHL disease accompanied by an interplay between neoplastic and autoimmune processes. Therefore, close monitoring of patients with clear cell NENs appears to be important before excluding VHL disease, even in the context of phenotypically unrelated diseases.

Do All Notochordal Lesions Require Proton Beam Radiotherapy? A Proposed Reclassification of Ecchordosis Physaliphora as Benign Notochord Cell Tumor.

Objectives Ecchordosis physaliphora (EP) is a benign notochord lesion of the clivus arising from the same cell line as chordoma, its malignant counterpart. Although usually asymptomatic, it can cause spontaneous cerebrospinal fluid (CSF) rhinorrhea. Benign notochordal cell tumor (BNCT) is considered another indolent, benign variant of chordoma. Although aggressive forms of chordoma require maximal safe resection followed by proton beam radiotherapy, BNCT and EP can be managed with close imaging surveillance without resection or radiotherapy. However, while BNCT and EP can be distinguished from more aggressive forms of chordoma, differentiating the two is challenging as they are radiologically and histopathologically identical. This case series aims to characterize the clinicopathological features of EP and to propose classifying EP and BNCT together for the purposes of clinical management. Design Case series. Setting Tertiary referral center, United Kingdom. Participants Patients with suspected EP from 2015 to 2019. Main Outcome Measures Diagnosis of EP. Results Seven patients with radiological suspicion of EP were identified. Five presented with CSF rhinorrhea and two were asymptomatic. Magnetic resonance imaging features consistently showed T1-hypointense, T2-hyperintense nonenhancing lesions. Diagnosis was made on biopsy for patients requiring repair and radiologically where no surgery was indicated. The histological features of EP included physaliphorous cells of notochordal origin (positive epithelial membrane antigen, S100, CD10, and/or MNF116) without mitotic activity. Conclusion EP is indistinguishable from BNCT. Both demonstrate markers of notochord cell lines without malignant features. Their management is also identical. We therefore propose grouping EP with BNCT. Close imaging surveillance is required for both as progression to chordoma remains an unquantified risk.

A novel case of paravertebral glomangiomyomatosis.

Glomangiomyomatosis is an extremely rare variant of glomus tumours. We describe the first known case of paravertebral glomangiomyomatosis in the literature to cause spinal cord compression. A 45-year old female patient presented with sudden onset of left leg pain and progressive weakness in left-sided hip flexion. An MRI spine revealed a large, lobulated, heterogeneous mass cantered on the left L2/3 foramen, mimicking a dumbbell nerve sheath tumour. The mass was invading the psoas muscle and displayed evidence of recent haemorrhage. The patient underwent debulking of the lesion via a left retroperitoneal approach. Surgery was uneventful, with clinical improvement and resolution of leg pain post-operatively. Histopathology of the tumour revealed delineated glomus-like cells and foci of spindled shaped cells resembling myoid differentiation. Immuno-histochemical features of the tumour confirmed the diagnosis of glomangiomyomatosis. The patient continued under close follow up, representing 18 months later with clinical and radiological progression of the disease with similar symptoms of leg pain but no weakness. Follow up MRI revealed progression of the intraspinal and paraspinal components of the tumour with thecal compression. A posterior approach was utilized in order to decompress the intraspinal component, which again was uneventful, and improved the patient's symptoms. This is the first known case of paravertebral glomangiomyomatosis in the literature and this rare entity should be considered in the differential diagnosis of nerve sheath tumours due to risk of progression and recurrence.

Inherited/Genetically-Associated Pheochromocytoma/ Paraganglioma Syndromes and COVID-19.

In some subjects with inherited pheochromocytoma/paraganglioma (PPG) syndromes, hypoxia-inducible factor 1 alpha (HIF1α) stabilization/activation could lead to an increase in angiotensin converting enzymes (ACE). This would result in the stimulation of angiotensin (AT) II production and, hence, reduce the availability of ACE 2. The latter would provide decreased numbers of binding sites for the spike protein of SARS-CoV-2 and, therefore, result in less points of viral entry into cells. Thus, subjects with HIF1α-associated PPG syndromes may benefit from an inherent protective effect against COVID-19. Such an implication of HIF1α vis-à-vis COVID-19 could open ways of therapeutic interventions.

Diabetes insipidus secondary to sellar/parasellar lesions.

Diabetes insipidus (DI) is a well-recognised transient or permanent complication following transsphenoidal surgery for pituitary adenomas or other sellar/parasellar lesions. However, data regarding the prevalence of pre-operative DI in sellar/parasellar lesions other than pituitary adenomas are scarce. We systematically reviewed the existing data for defining the prevalence of DI before any treatment in adult patients with sellar/parasellar lesions, excluding pituitary adenomas and metastatic lesions. In total, 646 patients with sellar/parasellar lesions presenting with DI at diagnosis were identified. The most common pathologies of sellar/parasellar lesions presenting with DI at diagnosis were lymphocytic hypophysitis (26.5%), craniopharyngiomas (23.4%), Langerhans's cell histiocytosis (18.9%) and Rathke's cleft cyst (12.7%), accounting for the vast majority (more than 80%) of these lesions. Overall, DI at diagnosis was found in 23.4% of all patients with sellar/parasellar lesions, albeit with a wide range from 10.6% to 76.7%, depending on the nature of the pathology. The highest prevalence of DI was found in less commonly encountered lesions namely germ-cell tumours (76.7%), abscesses (55.4%) and neurosarcoidosis (54.5%), each accounting for less than 3% of all sellar/parasellar lesions. Most DI cases (68.8%) were associated with anterior pituitary hormonal deficiencies, in contrast to pituitary adenomas that rarely present with DI. The enlargement and enhancement of the pituitary stalk were the most common findings on magnetic resonance imaging besides the loss of the high signal of the posterior pituitary on T1-weighted images. Resolution of DI spontaneously or following systemic and surgical management occurred in 22.4% of cases. Post-operative DI, not evident before surgery, was found in 27.8% of non-adenomatous sellar/parasellar lesions, and was transient in 11.6% of them. Besides distinctive imaging features and symptoms, early recognition of DI in such lesions is important because it directs the diagnosis towards a non-adenomatous sellar/parasellar tumour and the early initiation of appropriate treatment.

The natural history and treatment of non-functioning pituitary adenomas (non-functioning PitNETs).

Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism and manifestations attributed to mass effects on nearby structures. NFpitNETs follow generally an indolent course, but in 5-10% of cases they exhibit more aggressive behaviour, characterised by rapid growth, invasiveness and early recurrence. The initial size of the adenoma, the presence of symptoms and the histological subtype are related to the natural course of NFpitNETs. Active surveillance is usually the strategy of choice in the case of an asymptomatic NFpitNET, while surgical resection is recommended in case of visual and/or neurological abnormalities or rapid tumour growth. Based on previous and emerging data, approximately 50% of patients show tumour growth, while 20% of patients with NF-macroadenomas on active surveillance may require further intervention during a follow-up period of 7 years. Adjuvant radiotherapy is usually considered for large residual tumours or recurrent and/or aggressive adenomas, but there is evidence that medical therapy, especially with cabergoline, can occasionally be beneficial, whereas newer molecular agents are under investigation. Thus, while highly effective medical therapy is awaited, a move towards a more conservative approach seems appropriate, at least until we have better molecular markers of progressiveness.

Diffusion weighted image documented cerebral ischemia in the postprocedural period following pipeline embolization device with shield technology treatment of unruptured intracranial aneurysms: a prospective, single center study.

OBJECTIVE: Acute ischemic stroke and silent cerebral infarctions following pipeline embolization device (PED) treatment of intracranial aneurysms have been estimated to occur in 3-6% and in 50.9-90% of patients respectively. The PED with Shield technology (PED-Shield) incorporates a surface phosphorylcholine polymer to reduce the thrombogenicity of the implant. We sought to determine the incidence of diffusion weighted image (DWI) documented cerebral ischemia after PED-Shield treatment of unruptured intracranial aneurysms. METHODS: This prospective study involved a single center series of consecutive patients treated for an unruptured intracranial aneurysm with the PED-Shield. All participants underwent clinical evaluation on admission, after the procedure, at discharge, and 30 days following treatment. Brain MRI was obtained within 72 hours of the procedure. Ischemic lesions identified on DWI sequences where examined as to their number, size, and location in relation to the procedure. RESULTS: Over 12 months, 33 patients harboring 38 intracranial aneurysms were treated with the PED-Shield in 36 procedures. Neither mortality nor clinically evident ischemic events were noted in the 30 day postprocedural period. DWI documented, silent cerebral ischemia occurred in six patients (18.18%) after six procedures (16.66%). No statistically significant risk factors for postprocedural silent cerebral ischemia were identified. CONCLUSION: We demonstrated a reduced rate of silent cerebral infarcts following PED-Shield treatment of intracranial aneurysms than previously reported with other endovascular treatment modalities and with the previous device generations. Further research is necessary to evaluate our results and to identify methods to reduce the incidence of postprocedural cerebral ischemic events.

Spontaneous tension pneumocephalus and pneumoventricle in ecchordosis physaliphora: case report of a rare presentation and review of the literature.

We describe the case of a 65-year-old lady who presented with mutism and a right hemiparesis. Imaging showed a severe spontaneous tension pneumocephalus. The cause was diagnosed as Ecchordosis physaliphora (EP). EP is a rare cystic congenital hamartomatous benign notochordal tumor (BNCT) arising from an ectopic notochordal remnant. To the authors' knowledge, this is the first case of EP to be described in the literature which presented with a life-threatening but treatable condition of severe tension pneumocephalus.

Spinal myoclonus: a rare presentation of cervical myelopathy.

Myoclonus describes a movement disorder characterised by brief, abrupt and involuntary contractions of muscles or groups of muscles, usually associated with intracranial lesions, with limited evidence linking it to spinal pathologies. The pathophysiology of spinal myoclonus is extensive and multifactorial. Infection, intramedullary and extramedullary space-occupying lesions, trauma, vascular abnormalities, degenerative processes and cervical spondylosis have been implicated with the disease, the latter been associated with cervical stenosis with no reported cases linking it to an underlying cervical disc herniation. Although medical therapy with clonazepam, levetiracetam, valproate, tetrabenazine hydrochloride and spinal block injections has been equivocal, spinal myoclonus secondary to disc herniation requires surgical intervention. This report describes a case of segmental spinal myoclonus, secondary to a herniated cervical intervertebral disc. After corpectomy and a cage-augmented fusion technique, the myoclonic symptoms resolved. To our knowledge, this was the first report to describe the successful management of discogenic spinal myoclonus with spinal surgery.

Recurrent sampling and ventriculostomy-associated infections: a case-control study.

BACKGROUND: External ventricular drain (EVD) insertion is a common neurosurgical procedure with a significant risk of ventriculostomy-associated infections (VAIs), other morbidities and mortality. Several risk factors have been identified but their effect is unclear. OBJECTIVE: Our primary objective was to assess whether recurrent EVD sampling increased the risk of VAIs. The secondary objective was to explore the effect of sampling frequency, duration of EVD stay, presence of cerebrospinal fluid leak and concurrent infections. METHODS: Ours was a retrospective, single-centre, age-matched, case control study of 83 patients and 249 controls who underwent EVD insertion between 1 January 2010 - 31 December 2016. Patients with primary CNS infections, age under 1 year and death within 5 days of EVD insertion were excluded. Blinded abstractors collected all patient data through the electronic patient record system and regression analysis was used to compare the two groups. RESULTS: Sampling the EVD more than once did not increase the risk of infection (OR 0.47, 95% CI 0.27-0.83, p = 0.01). Risk factors significantly associated with VAI included CSF leak (OR 2.06, 95% CI 1.16-3.67, p = 0.01), concurrent infection (OR 1.85, 95% CI 1.09-3.16, p = 0.02), and an EVD duration of >10 days (OR 2.28, 95% CI 1.24-4.18, p = 0.01). CONCLUSION: Our findings do not support the notion that increased sampling of EVDs is associated with a higher risk of VAI. CSF leaks, concurrent infection and long-term EVDs are also statistically significant risk factors for infection.