Examples on the different types of infection.

<p>A) Superficial incisional SSI. B) Deep incisional SSI. C) Organ/space SSI. (SSI = surgical site infection).</p

Number of infections in relation to possible risk factors.

<p>(M = male, F = female).</p><p>*21 with unknown smoking status.</p

Number of days until onset of infection compared with culture results.

<p>S. aureus infections have earlier onset than in the CoNS group (p-value 0.02, Mann-Whitney U Test). (S. Aureus = Stahylococcus Aureus, CoNS = coagulase negative staphylococci).</p

Data on all the cases of infection.

<p>(M = male, F = female, PD = Parkinson’s disease, Dy = dystonia (primary), ET = essential tremor, PKAN = pantothenate kinase-associated neurodegeneration, STN = nucleus subthalamicus, ViM = ventral intermediate nucleus of thalamus, GPi = internal globus pallidus, IPG = Implanted Pulse Generator, replacem = replacement, reimpl = reimplantation, postaur = postauricular, R = right, L = left, S. aureus = Staphylococcus aureus, CoNS = coagulase-negative Staphylococci (includes S. epidermidis and S. capitis), NA = not applicable (test not obtained), B = bilateral).</p

Infection treatment flowchart.

<p>Infection treatment flowchart.</p

Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia

<div><p>Hereditary ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early and late-onset hereditary ataxia and spastic paraplegia probands, in whom extensive previous investigations had failed to identify the genetic cause of disease. Pathogenic and likely-pathogenic variants were identified in 20 probands (19%) and variants of uncertain significance in ten probands (10%). Together these accounted for 30 probands (29%) and involved 18 different genes. Among several interesting findings, dominantly inherited <i>KIF1A</i> variants, p.(Val8Met) and p.(Ile27Thr) segregated in two independent families, both presenting with a pure spastic paraplegia phenotype. Two homozygous missense variants, p.(Gly4230Ser) and p.(Leu4221Val) were found in <i>SACS</i> in one consanguineous family, presenting with spastic ataxia and isolated cerebellar atrophy. The average disease duration in probands with pathogenic and likely-pathogenic variants was 31 years, ranging from 4 to 51 years. In conclusion, this study confirmed and expanded the clinical phenotypes associated with known disease genes. The results demonstrate that gene panel sequencing and similar sequencing approaches can serve as efficient diagnostic tools for different heterogeneous disorders. Early use of such strategies may help to reduce both costs and time of the diagnostic process.</p></div

Clinical flowchart.

<p>The figure explains the selection of probands from the clinicogenetic database, and the resulting total number of molecular diagnoses. VUS: variants of uncertain significance. * Indicates selection criteria of 105 probands: 1) Verified family history; 2) Completed thorough investigations; 3) Availability of probands; 4) Sporadic cases considered to be HSP or HA, fulfilling 2) and 3).</p

Clinical characteristics of the 105 probands included in the study.

<p>Clinical characteristics of the 105 probands included in the study.</p

Pedigree structures of families with <i>KIF1A</i> variants.

<p>(a) Pedigree structure of family HCT-024 (III-7) with a c.80T>C, p.(Ile27Thr) variant in <i>KIF1A</i>. The filled symbols indicate affected individuals. The striped symbol indicates an individual that was initially classified as a non-affected individual, but after clinical re-examination was also found to be possibly affected. (b) Pedigree structure of family of HCT-026 (IV-6) with a c.22G>A, p.(Val8Met) variant. The symbols with a question mark are not confirmed regarding the phenotype. The diamond shaped symbols indicate masked gender. A line crossing a symbol represents a deceased individual. Probands are labelled with ‘P’.</p

Pedigree structure and MRI scans of a family with <i>SACS</i> variants.

<p>(a) Pedigree structure of family HCT-106 (V-3) with a c.12688G>A, p.(Gly4230Ser) and c.12661C>G, p.(Leu4221Val) variants in <i>SACS</i>. A consanguineous marriage between individuals IV-2 and III-4 is indicated by a double line. Cerebral MRIs of HCT-106 at disease duration of 28 years in (b) FLAIR sequence in midline sagittal plane, (c) FLAIR sequence in coronal plane at the level of dorsal aspect of cerebellum, (d) FLAIR sequence in transversal plane at the level of the middle cerebellar peduncles, and (e) T2 sequence in transversal plane at the level of the superior cerebellar peduncles, showing atrophy of the cerebellar hemispheres and vermis with widening of fissures and folia.</p