Cerebellar Cortex Stimulation for Acquired Dystonia: A Case Report and Review of Its Role in Modern Surgical Practice.

BACKGROUND: Cerebral palsy (CP) is a common cause of acquired dystonia, which can lead to significant interference with quality of life and societal participation. In the last two decades, the surgical treatment of dystonia has primarily focused on deep brain stimulation targeting the basal ganglia and thalamic circuits. However, stimulation of the basal ganglia has generally been less effective in acquired combined forms of dystonia, including dystonic CP. These limitations, along with growing evidence for the role of the cerebellum in the pathophysiology of dystonia, have led to renewed interest in the cerebellum as a target for therapeutic stimulation in dystonia. Nevertheless, there are very few contemporary studies demonstrating its use. We present the case of a patient with generalized dystonia due to dyskinetic CP who was successfully treated with stimulation of the cerebellar cortex in the modern era. We also review the evidence underpinning targeting of the cerebellum in surgical therapy for dystonia and examine the latest reports of this approach in the surgical literature. SUMMARY: The patient derived significant improvement in the control of her dystonic symptoms, with a reduction in her BFMDRS score from 83 to 25. No complications were observed during more than 3 years of postoperative follow-up. Since the turn of the 21st century, there have been only 7 reports of cerebellar stimulation for dystonia, recruiting a total of 18 patients. These studies have exclusively targeted deep brain structures, making the present report of cortical cerebellar stimulation particularly unique. KEY MESSAGES: In the 21st century, cerebellar stimulation has predominantly been a second-line treatment for dystonia, after the failure of DBS targeting more mainstream loci within the thalamus and globus pallidus. However, there is increasing recognition of the role of the cerebellum in movement disorders, with multiple convergent lines of evidence supporting its involvement in dystonia pathophysiology. The cerebellum is worthy of greater consideration as a target for neurostimulation in dystonia, particularly in cases of acquired etiology.

Low but not undetectable early postoperative nadir serum cortisol predicts sustained remission in Cushing's disease.

Objective: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease. The objectives of the study were to determine remission and recurrence rates after TSS for Cushing's disease, identify factors that predict these outcomes, and define the threshold for postoperative morning serum cortisol (MSeC) that most accurately predicts sustained remission. Methods: Records were retrospectively reviewed for consecutive adults undergoing TSS for Cushing's disease at a tertiary centre (1990-2019). Remission was defined as MSeC <138 nmol/L by 6 weeks postoperatively. Recurrence was defined as elevated 24-h urine free cortisol, lack of suppression after dexamethasone or elevated midnight salivary cortisol. Results: In this study, 42 patients (age 47 ± 13 years, 83% female) were assessed with 55 ± 56 months of follow-up. Remission occurred after 77% of primary (n = 30) and 42% of revision operations (n = 12). After primary surgery, remission was associated with lower MSeC nadir (26 ± 36 nmol/L vs 347 ± 220 nmol/L, P < 0.01) and lower adrenocorticotropin nadir (2 ± 3 pmol/L vs 6 ± 3 pmol/L, P = 0.01). Sustained remission 5 years after surgery was predicted by MSeC <92 nmol/L within 2 weeks postoperatively (sensitivity 100% and specificity 100%). After revision surgery, remission was predicted by lower MSeC nadir (70 ± 45 nmol/L vs 408 ± 305 nmol/L, P = 0.03), smaller tumour diameter (3 ± 2 mm vs 15 ± 13 mm, P = 0.05) and absence of cavernous sinus invasion (0% vs 71%, P = 0.03). Recurrence after primary and revision surgery occurred in 17% and 20% of patients respectively. Conclusions: Lower postoperative MSeC nadir strongly predicted remission after both primary and revision surgery. Following primary surgery, an MSeC <92 nmol/L within 2 weeks predicted sustained remission at 5 years. MSeC nadir was the most important prognostic marker following TSS for Cushing's disease.

Sinus Radiological Findings in General Asymptomatic Populations: A Systematic Review of Incidental Mucosal Changes.

OBJECTIVE: To determine the range of incidental mucosal changes in a general sinonasally asymptomatic population on radiology. DATA SOURCES: Medline (1996-present) and Embase (1974-present) were searched on March 14, 2020, to identify articles that reported radiological sinus mucosal findings in asymptomatic population groups. Bibliographic search of included studies was conducted to identify additional articles. REVIEW METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive search strategy was formulated and articles screened to extract data reporting Lund-Mackay (LM) score, presence of mucous retention cysts, and maxillary mucosal thickening. A random-effects model was used in meta-analysis. RESULTS: A total of 950 articles were identified, of which 33 manuscripts met the inclusion criteria. The included studies involved 16,966 sinonasally asymptomatic subjects. The mean LM score was 2.24 (95% CI, 1.61-2.87), and an LM score of ≥4 in 14.71% (95% CI, 6.86-24.82%) was present across all general asymptomatic population groups. Mucous retention cysts were noted in 13% (95% CI, 8.33-18.55%) and maxillary mucosal thickening of ≥2 mm in 17.73% (95% CI, 8.67-29.08%). CONCLUSION: The prevalence of incidental mucosal changes in a general asymptomatic population on radiology needs to be considered when making a diagnosis of chronic rhinosinusitis.

Nasal Peak Inspiratory Flow in Healthy and Obstructed Patients: Systematic Review and Meta-Analysis.

OBJECTIVES: Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta-analysis was to determine the mean NPIF value in populations with and without nasal obstruction. METHODS: Medline (1946-) and Embase (1947-) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta-analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]). RESULTS: The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9-148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1-108.8) L/min. CONCLUSIONS: Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260-267, 2021.

Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded. RESULTS: The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 µg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. CONCLUSIONS: TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L).

Diagnosing Cushing's disease in the context of chronic kidney disease: a case report and literature review.

OBJECTIVE: The diagnosis of Cushing's disease (CD) is particularly challenging in patients with chronic kidney disease (CKD) due to abnormalities of the hypothalamo-pituitary-adrenal axis associated with the latter. This case report presents discrepant biochemical findings in a patient with CKD who was subsequently diagnosed with CD, and outlines principles which may guide the definitive diagnosis of CD in this context. METHODS: The case of a patient with Stage 4 CKD who underwent transsphenoidal surgery for pituitary-dependent CD is presented. A literature review was conducted to identify similar cases and characterise features of hypothalamo-pituitary-adrenal axis dysfunction in CKD. RESULTS: The patient discussed herein presented with markedly elevated plasma adrenocorticotrophic hormone (ACTH) due to a pituitary macroadenoma, with normal 24-h urine free cortisol (24-UFC) but abnormal overnight dexamethasone suppression testing and elevated midnight salivary cortisol. He experienced biochemical remission after undergoing transsphenoidal adenomectomy. A literature review revealed that CKD can be associated with elevated serum cortisol, reduced UFC and elevated plasma ACTH. Only four other cases of CD being diagnosed in a patient with CKD have been published. The loss of a circadian rhythm of cortisol secretion was the most common feature among all cases. CONCLUSIONS: To establish a definitive diagnosis of CD in the context of pre-existing CKD, the absence of circadian rhythms of cortisol and ACTH is a more sensitive indicator than 24-UFC and low-dose dexamethasone suppression testing.