Sensory profiles in women with neuropathic pain after breast cancer surgery.

PURPOSE: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). METHODS: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. RESULTS: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. CONCLUSIONS: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.

Patients with complex regional pain syndrome overestimate applied force in observed hand actions.

BACKGROUND: Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. METHODS: Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. RESULTS: The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. CONCLUSIONS: We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance.

Depression, anxiety, and cognitive functioning after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) is an important complication of stroke. We studied long-term PSD after intracerebral hemorrhage (ICH) at young age, as well as anxiety, and cognitive functioning of the survivors. METHODS: We gathered clinical and imaging data of 336 young ICH patients between age 16 and 49 treated in the Helsinki University Central Hospital. After a median follow-up of 9.7 (7.0-12.0) years, we interviewed 130 survivors with structural questionnaires including Beck Depression Inventory II (BDI-II), Hospital Anxiety and Depression Scale (HADS), Pain Anxiety Symptoms Scale (PASS), Brief Pain Inventory (BPI), and Montreal Cognitive Assessment (MoCA). Univariate and multivariate analysis was performed to identify factors associated with PSD (BDI-II score >13). Degree of disability was measured by modified Rankin Scale score (mRS). RESULTS: PSD was present among 30 (23.1%) and anxiety among 52 (40.0%) patients (HADS score >6). Higher degree of disability was associated with symptoms of depression (higher BDI-II scores, P = 0.001), emotional distress (higher HADS scores, P = 0.004), and pain (higher PASS scores, P = 0.008, and higher BPI scores, P = 0.003). The only baseline factor identified to associate with PSD was hydrocephalus (P = 0.014). Median PASS score was 9 (IQR 0-25), median BPI score was 5 (0-23), and median MoCA score was 26 (22-28) hinting to normal or mild cognitive dysfunction. Antidepressants were used by 9.2%. CONCLUSIONS: One of four survivors of ICH at young age suffers long-term PSD. Higher degree of disability predicted occurrence of PSD. Treatment of depression appears as an unmet need in young ICH survivors.

Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura.

Among the few independently replicated genetic associations in migraine are polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and oestrogen receptor (ESR1) genes. We studied the contribution of these genes to migraine susceptibility by genotyping six MTHFR and 26 ESR1 polymorphisms in 898 unrelated migraine with aura (MA) patients and in 900 unrelated healthy controls. There were no differences in the genotype distributions of the previously migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and controls (P-values 0.83 and 0.55, respectively). Thus, we were not able to replicate the previous findings, although our study had considerable power. However, five of the ESR1 SNPs (rs6557170, rs2347867, rs6557171, rs4870062 and rs1801132) that were in strong linkage disequilibrium were nominally associated with MA (uncorrected P-values 0.007-0.034). These results did not, however, remain significant after taking multiple testing into account. Thus it seems unlikely that the studied genes are involved in migraine susceptibility, at least in this sample.

Decreased cerebellar total creatine in episodic ataxia type 2: a 1H MRS study.

Episodic ataxia type 2 (EA2) affects mainly the cerebellum via mutations in the CACNA1A gene. The authors used proton MR spectroscopy to examine cerebellar and thalamic metabolism of nine mostly nonataxic EA2 family members (all with proven CACNA1A mutation) and nine healthy control subjects. Cerebellar total creatine was lower in the patient group (p = 0.005) than in control subjects, possibly reflecting an early sign of calcium channel dysfunction in EA2.

A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2.

Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in the Na+K+-ATPase alpha2 subunit gene, ATP1A2, on 1q23 have recently been shown to cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions of this gene in a Finnish chromosome 1q23-linked FHM family with associated symptoms such as coma and identified a novel A1033G mutation in exon 9. This mutation results in a threonine-to-alanine substitution at codon 345. This residue is located in a highly conserved N-terminal region of the M4-5 loop of the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the disorder in our family and was not present in 132 healthy Finnish control individuals. For these reasons it is most likely the FHM-causing mutation in this family.

Novel splice site CACNA1A mutation causing episodic ataxia type 2.

Episodic ataxia type 2 (EA-2) is an autosomal dominant neurological disorder, characterized by episodes of ataxia, vertigo, nausea, nystagmus, and fatigue, associated with acetazolamide responsiveness. The disease is caused by mutations in the P/Q-type calcium channel Ca(v)2.1 subunit gene, CACNA1A, located on chromosome 19p13.2. We analyzed a family with 13 affected individuals for linkage to this locus and reached a two-point maximum LOD score of 4.48. A novel CACNA1A mutation, IVS36-2A>G, at the 3' acceptor splice site of intron 36 was identified by sequencing. It is the first described CACNA1A acceptor splice site mutation and the most C-terminal EA-2-causing mutation reported to date.

Subclinical vestibulocerebellar dysfunction in migraine with and without aura.

OBJECTIVE: In patients with migraine, neurotologic symptoms and signs occur commonly. The authors' aim was to determine whether neurotologic findings are in accordance with the type of migraine and whether test findings differ from those of healthy controls. METHODS: The authors examined 36 patients with various types of migraine classified by International Headache Society criteria. Comprehensive neurotologic tests were performed between attacks: video-oculography (VOG), electronystagmography, static posturography, and audiometry on 12 patients with migraine with aura (MA) and 24 patients with migraine without aura (MO). Results were compared to those of test-specific nonmigrainous control groups. Only eight migraineurs (six with MA and two with MO) had vertigo or dizziness. RESULTS: Despite the absence of clinical neurotologic symptoms, most of the patients with migraine (83%) showed abnormalities in at least one of these tests. Both migraine types differed significantly from the control group (in VOG, in saccadic accuracy, and in static posturography). Vestibular findings tended to be more severe in MA than in MO. CONCLUSIONS: These data suggest that interictal neurotologic dysfunction in MA and MO share similar features and that the defective oculomotor function is mostly of vestibulocerebellar origin.