The NF1 microdeletion syndrome: early genetic diagnosis facilitates the management of a clinically defined disease.

Neurofibromatosis type-1 (NF1) is a genodermatosis frequently encountered in general dermatology. In many patients, the diagnosis of NF1 is made clinically based on the presence of café-au-lait macules and skinfold freckling, as well as plexiform neurofibromas detectable during early childhood. Later in life, cutaneous neurofibromas often represent important diagnostic features. NF1 is characterized by extreme clinical variability and a broad heterogeneity of NF1 gene mutations which impede genotype/phenotype correlations. Notable exceptions are NF1 microdeletions observed in 5-11 % of all NF1 patients. Patients with NF1 microdeletions frequently exhibit facial dysmorphic features and a tall stature as rather specific clinical signs. Furthermore, cutaneous and subcutaneous neurofibromas present at an early age, severe global developmental delay and cognitive disability are pathognomonic for the "NF1 microdeletion syndrome". Importantly, NF1 microdeletions are associated with an approximately twofold higher risk for malignant peripheral nerve sheath tumors than intragenic NF1 gene mutations. The severe clinical manifestations of patients with NF1 microdeletions require early multidisciplinary clinical care and frequent tumor surveillance. Therefore, when red flag features for the "NF1 microdeletion syndrome" are present in a patient, genetic testing is necessary to confirm or exclude an NF1 microdeletion.

Das NF1-Mikrodeletions-Syndrom: Die frühzeitige genetische Diagnose erleichtert den Umgang mit einer klinisch definierten Erkrankung.

Neurofibromatose Typ-1 (NF1) ist ein Genodermatose, die häufig in der Dermatologie behandelt wird. Bei vielen Patienten mit NF1 wird die Diagnose aufgrund klinischer Merkmale erstellt wie Café-au-Lait-Flecken, Freckling und plexiformen Neurofibromen, die schon während der frühen Kindheit auftreten können. Später im Leben sind oft kutane Neurofibrome weitere wichtige diagnostische Merkmale. Die NF1 ist durch ausgeprägte klinische Variabilität und eine breite Heterogenität der NF1-Genmutationen charakterisiert, was Genotyp/Phänotyp-Korrelationen erschwert. Wichtige Ausnahmen sind NF1-Mikrodeletionen, die bei 5-11 % aller NF1-Patienten auftreten. Patienten mit NF1-Mikrodeletionen zeigen häufig spezifische Merkmale wie Gesichtsdysmorphien und sind von großer Statur. Zudem sind früh auftretende kutane und subkutane Neurofibrome, schwere Entwicklungsverzögerungen in multiplen Bereichen sowie kognitive Einschränkungen pathognomonisch für das NF1-Mikrodeletions-Syndrom. Darüber hinaus sind NF1-Mikrodeletionen mit einem Risiko für maligne periphere Nervenscheidentumoren assoziiert, das etwa zweifach höher ist als bei intragenischen NF1-Mutationen. Die schweren klinischen Manifestationen bei Patienten mit NF1-Mikrodeletionen machen eine frühe multidisziplinäre klinische Betreuung und häufige Tumor-Überwachung der Patienten notwendig. Wenn bei einem Patienten Red-Flag-Symptome für das NF1-Mikrodeletions-Syndrom auftreten, ist eine frühzeitige genetische Untersuchung notwendig, um eine NF1-Mikrodeletion zu bestätigen oder auszuschließen.

The impact of SARS-Covid-19 pandemic on peripheral nerve surgery - A single centre report.

OBJECTIVE: SARS-Cov-19 pandemic totally changed daily routine work in German hospitals. As hospital capacity was reduced, many surgeries were postponed or even cancelled. On March 25th 2020 the German Society of Neurosurgery (DGNC) published a statement in which urgent non-elective surgeries were defined for each neurosurgical domain, whereas elective interventions were deferred. The present work examines the impact of these Covid strategies focusing on patients with peripheral lesions who were conducted to our department during this period of time. METHODS: All patients who underwent any peripheral nerve surgery at our department from January 2018 until December 2022, were included. The complete range of surgeries including peripheral nerve lesions was examined encompassing compression syndromes, traumatic lesions of brachial plexus, traumatic lesions and tumors of single peripheral nerves. The numbers of surgical procedures were compared before, during and after pandemic. Pearson correlation coefficient was analysed. RESULTS: From 2018 to 2022 the total number of surgical procedures involving peripheral nerves included 2422 procedures. Compression syndromes made up the largest proportion (1433 operations, 59%), followed by peripheral nerve lesions (445 operations, 18%), peripheral nerve tumors (344 operations, 14%) and lesions of the brachial plexus (142 operations, 6%). The average was 40,5 interventions per month, the range was 7-63. Two declines in the number of peripheral nerve surgeries were noted during this period. The first was in April and May 2020 with an average drop of 65% and 41% respectively. In these months the average number of operations was 37. The second decrease was from October 2021 until January 2022, where number of surgeries was reduced by 16%, 36%, 83% and 18% with an average number of 50 operations. Both declines showed a significant and strong correlation with the lower number of compression syndrome treatments (r = 0.952, p < 0.001 and r = 0.968, p < 0.001), while no drop and no significant correlation was found in the treatment of traumatic peripheral nerve injuries (p = 0.769, r = 0.095 and p = 0.243, r = 0.366) and traumatic brachial plexus injuries (p = 0.787, r = 0.088 and p = 0.780, r = 0.09). A weak significant correlation was seen in the treatment numbers of peripheral nerve tumors (p = 0.017, r = 0.672 and p = 0.015, r = 0.67). CONCLUSION: Covid-19 pandemic lead to a significant decrease in the number of nerve decompressions, since, according to the German Society of Neurosurgery, those were considered as elective surgeries.

Clinical outcome after decompression of intraneural peroneal ganglion cyst and its morphologic correlation to postoperative nerve ultrasound.

OBJECTIVE: Intraneural ganglion cysts are rare and benign mucinous lesions that affect peripheral nerves, most frequently the common peroneal nerve (CPN). The precise pathophysiological mechanisms of intraneural ganglion cyst development remain unclear. A well-established theory suggests the spread of mucinous fluid along the articular branch of the peroneal nerve as the underlying mechanism. Clinical outcome following decompression of intraneural ganglion cysts has been demonstrated to be excellent. The aim of this study was to evaluate the correlation between clinical outcome and ultrasound-detected morphological nerve features following decompression of intraneural ganglion cysts of the CPN. METHODS: Data were retrospectively analyzed from 20 patients who underwent common peroneal nerve ganglion cyst decompression surgery at the Universität Ulm/Günzburg Neurosurgery Department between October 2003 and October 2017. Postoperative clinical outcome was evaluated by assessment of the muscular strength of the anterior tibial muscle, the extensor hallucis longus muscle, and the peroneus muscle according to the Medical Research Council grading system. Hypesthesia was measured by sensation testing. In all patients, postoperative morphological assessment of the peroneal nerve was conducted between October 2016 and October 2017 using the iU22 Philips Medical ultrasound system at the last routine follow-up appointment. Finally, the correlations between morphological changes in nerve ultrasound and postoperative clinical outcomes were evaluated. RESULTS: During the postoperative ultrasound scan an intraneural hypoechogenic ring structure located at the medial side of the peroneal nerve was detected in 15 (75%) of 20 patients, 14 of whom demonstrated an improvement in motor function. A regular intraneural fasicular structure was identified in 3 patients (15%), who also reported recovery. In 1 patient, a recurrent cyst was detected, and 1 patient showed intraneural fibrosis for which recovery did not occur in the year following the procedure. Two patients (10%) developed neuropathic pain that could not be explained by nerve ultrasound findings. CONCLUSIONS: The results of this study demonstrate significant recovery from preoperative weakness after decompression of intraneural ganglion cysts of the CPN. A favorable clinical outcome was highly correlated with an intraneural hypoechogenic ring-shaped structure on the medial side of the CPN identified during a follow-up postoperative ultrasound scan. These study results indicate the potential benefit of ultrasound scanning as a prognostic tool following decompression procedures for intraneural ganglion cysts of the CPN.

Determining the utility of intraoperative magnetic resonance imaging for transsphenoidal surgery: a retrospective study.

OBJECT: Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI. METHODS: A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors' institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension. RESULTS: The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown. CONCLUSIONS: The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.