Purpose To determine the value of combined 18 F-FDG PET/CT with diagnostic contrast-enhanced CT (CECT) in detecting primary malignancies and metastases in patients with paraneoplastic neurological syndromes (PNS) and to compare this with CECT alone. Methods PET/CT scans from 66 patients with PNS were retrospectively evaluated. Two blinded readers initially reviewed the CECT portion of each PET/CT scan. In a second session 3 months later, the readers analysed the combined PET/CT scans. Findings on each study were assessed using a four-point-scale (1 normal/benign; 2 inconclusive, further diagnostic work-up may be necessary; 3 malignant; 4 inflammatory). Sensitivity and specificity for malignant findings were calculated for PET/CT and CECT. Interreader agreement was determined by calculating Cohen’s kappa. Pooled data from clinical follow-up (including histopathology and follow-up imaging, median follow-up 20.0 months) served as the reference gold standard. Results Both readers classified 12 findings in ten patients (15 %) as malignant on the PET/CT scans (two patients had two primary tumours). One such imaging finding (suspected thymic cancer) was false-positive (i.e. benign histology). The most common tumours were bronchial carcinoma ( n = 3), lymph node metastases of gynaecological tumours ( n = 3) and tonsillar carcinoma ( n = 2). Three of 12 findings (25 %) were not detected by CECT alone (cervical carcinoma, lymph node metastasis and tonsillar carcinoma). In a per-patient analysis, sensitivity and specificity for malignant findings were 100 % and 90 % for PET/CT and 78 % and 88 % for CECT. In 24 % (reader 1) and 21 % (reader 2) of the patients, the PET/CT findings were inconclusive. Of these findings, 57 % (reader 1) and 56 % (reader 2) were only diagnosed with PET (e.g. focal FDG uptake of the thyroid, gastrointestinal tract and ovaries). On follow-up, none of these findings corresponded to malignancy. Overall agreement between the two readers was excellent with a Cohen’s kappa of 0.95 ± 0.04 ( p < 0.001) for PET/CT and 0.97 ± 0.03 ( p < 0.001) for CECT alone. Conclusion In this cohort of patients with PNS, PET/CT exhibited improved detection of underlying malignancy versus CECT alone. While hybrid imaging produces a greater number of inconclusive findings, sensitivity is increased for the detection of head and neck and gynaecological malignancies as well as metastatic lymph node involvement.

Ziele: Ziel der Studie war, die Rolle der 18F-FDG-PET-CT zum Nachweis von Primärtumoren und Metastasen bei Patienten mit paraneoplastischen neurologischen Syndromen (PNS) im Vergleich zur kontrastverstärkten CT (KM-CT) zu evaluieren. Methode: PET-CT von 66 Patienten mit PNS (z.B. limbische Enzephalitis) wurden retrospektiv ausgewertet. Zunächst beurteilten 2 geblindete Reviewer die KM-CT-Komponente alleine; in einer 2. Sitzung 3 Monate später wurden die vollständigen PET-CT-Untersuchungen analysiert. Befunde wurden anhand einer 4-Punkt-Skala beurteilt (1: normal/gutartig; 2: unklar, weitere diagnostische Abklärung nötig; 3: maligne; 4: entzündlich). Die Ergebnisse wurden zu den klinischen Daten aus den Patientenakten korreliert. Ergebnis: 12 Befunde bei 10/66 (15,2%) Patienten wurden alle korrekt als maligne im PET-CT klassifiziert (2 Patienten mit jeweils 2 Primärtumoren). Die häufigsten Tumore waren Lungenkarzinome (n:3); Lymphknotenmetastasen von gynäkologischen Tumoren (n:3) und Tonsillenkarzinome (n:2). 3/12 (25%) der Malignome wurden im KM-CT nicht detektiert (Cervixkarzinom, Lymphknotenmetastase, Tonsillenkarzinom). Allerdings wurden bei 16/66 (24,2%) Patienten 21 Befunde als unklar klassifiziert. 57% dieser Befunde wurden nur durch die PET-Komponente diagnostiziert (z.B. fokale FDG-Aufnahme in Schilddrüse, Darm, Ovarien). In keinem dieser Fälle wurde im klinischen Verlauf ein Malignom gefunden. Schlussfolgerung: Mit der PET-CT wurden die ursächlichen Malignome in 15,2% der Patienten mit PNS korrekt detektiert. Die Hybridbildgebung war der alleinigen KM-CT überlegen. Auch wenn durch unklare PET-Befunde relativ häufig eine weitere diagnostische Abklärung verursacht wird, erhöht die PET-Komponente die diagnostische Genauigkeit insbesondere bei Kopf-Hals- und gynäkologischen Tumoren sowie Lymphknotenmetastasen.

Hemiplegic migraine (HM) is a rare and severe subtype of migraine with aura, characterized by some degree of hemiparesis and other aura symptoms. Mutations in three genes (CACNA1A, ATP1A2 and SCN1A) have been detected in familial and, more rarely, in sporadic cases. The disease can be complicated by permanent neurological deficits, the most frequent one being a cerebellar syndrome; in addition, mental retardation has been recognized as part of the phenotypic spectrum. Here, we report a Caucasian male with a novel CACNA1A mutation and an unusual clinical phenotype: the patient, who had had a history of only two HM attacks, sought medical advice at age 49 primarily because of increasing cognitive decline accompanied by cerebellar dysfunction. While common neurodegenerative causes were excluded, neuropsychological evaluation revealed a distinct profile of deficits of a subcortico-prefrontal type as previously reported in patients with cerebellar dysfunction. This suggests a possible causal link between cerebellar and cognitive disturbances in this patient; in addition to these pathophysiological aspects, we review of the role of the cerebellum in cognition.

Introduction Cholesterol crystal embolism complicating arterial catheterization usually presents as a multiorgan disease with renal failure, abdominal problems, and skin manifestations.Methods We present a patient with hypertension and generalized arteriosclerosis who presented with muscle weakness, diffuse pain in the extremities, and renal failure 3 weeks after coronary catheterization and angioplasty of the right coronary artery. Muscle weakness progressed during the following months.Results Nerve conduction studies and nerve biopsy showed severe axonal nerve injury. Biopsy of the kidney revealed the diagnosis of cholesterol crystal embolism.Conclusion The clinical presentation indicates a direct association of cholesterol crystal embolism and polyneuropathy. Although cholesterol crystal embolism represents a rare cause of polyneuropathy, it should be considered in patients with acute onset polyneuropathy and sudden onset multiorgan disease after arterial catheterization.

Background: The definite diagnosis of acute Lyme neuroborreliosis (LNB) requires detection of an increased Borrelia burgdorferi–specific antibody index (AI). The B burgdorferi AI, however, is negative in up to 20% of patients with early LNB and can remain elevated for years after adequate therapy; both of these factors can make the diagnosis difficult. Recent retrospective studies suggested the chemokine CXCL13 as a potential biomarker for LNB. To evaluate its diagnostic value, we conducted a prospective study. Methods: From March 2008 to August 2009, CSF and serum samples from all patients in whom a B burgdorferi–specific AI was requested (n = 692) and CSF analysis revealed CSF pleocytosis (n = 192) were included in the study. Because of the low number of patients with untreated LNB, 13 additional retrospectively selected samples of patients with untreated LNB were added. CXCL13 concentrations were measured by ELISA and receiver operating characteristic curves were generated. Results: CSF CXCL13 was highly elevated in all patients with untreated acute LNB (mean = 15,149 pg/mL) compared with that in the patients without LNB (mean = 247 pg/mL). At a cutoff of 1,229 pg/mL, the sensitivity of CXCL13 was 94.1%, which is higher than the AI (85.7%). Only 7 patients (5 with a CNS lymphoma and 2 with bacterial meningitis) had a CXCL13 level above the cutoff, resulting in a specificity equal to the AI of 96.1%. Conclusions: CXCL13 shows high sensitivity and specificity for acute, untreated LNB. This novel marker appears to be helpful in clinically atypical cases and, in particular, in early stages of the disease when the B burgdorferi AI is (still) negative.

The mitochondrial 12S rRNA is considered a hotspot for mutations associated with nonsyndromic (NSHL) and aminoglycoside-induced hearing loss (AIHL). Although aminoglycoside ototoxicity is the most common cause of bilateral vestibular dysfunction, the conceivable role of 12S rRNA mutations has never been systematically investigated. We sequenced the 12S rRNA of 66 patients with bilateral vestibulopathy (BV) with (n=15) or without (n=51) prior exposure to aminoglycosides, as well as 155 healthy controls with intact vestibular function (sport pilots), and compared these to 2704 published sequences (Human Mitochondrial Genome Database). No mutations with a confirmed pathogenicity were found (A1555G, C1494T), but four mutations with a hitherto tentative status were detected (T669C, C960del, C960ins, T961G). Due to their predominant occurrence in patients without aminoglycoside exposure, their detection in controls and a weak evolutionary conservation, their pathogenic role in vestibulocochlear dysfunction remains provisional.