Fredrik Lundin

Incidence and outcome of surgery for adult hydrocephalus patients in Sweden

Abstract Object: To present population-based and age related incidence of surgery and clinical outcome for adult patients operated for hydrocephalus, registered in the Swedish Hydrocephalus Quality Registry (SHQR). Methods: All patients registered in SHQR during 2004–2011 were included. Data on age, gender, type of hydrocephalus and type of surgery were extracted as well as three months outcome for patients with idiopathic normal pressure hydrocephalus (iNPH). Results: The material consisted of 2360 patients, 1229 men and 1131 women, age 63.8 ± 14.4 years (mean ± standard deviation (SD)). The mean total incidence of surgery was 5.1 ± 0.9 surgeries/100,000/year; 4.7 ± 0.9 shunt surgeries and 0.4 ± 0.1 endoscopic third ventriculostomies. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus, the incidence of surgery was 2.2 ± 0.8, 1.9 ± 0.3 and 0.8 ± 0.1/100,000/year, respectively. During 2004–2011, the incidence of surgery increased in total (p = .044), especially in age groups 70–79 years and ≥80 years (p = .012 and p = .031). After surgery, 253 of 652 iNPH patients (38.8%) improved at least one step on the modified Rankin scale (mRS). Number needed to treat was 3.0 for improving one patient from unfavourable (mRS 3–5) to favourable (mRS 0–2). The mean score of a modified iNPH scale increased from 54 ± 23 preoperatively to 63 ± 25 postoperatively (p < .0001, n = 704), and 58% improved. No significant regional differences in incidence, surgical techniques or outcome were found. Conclusions: Incidence of hydrocephalus surgery increased significantly during 2004–2011, specifically in elderly patients. Surgical treatment of iNPH markedly improved functional independence, but the improvement rate was low compared to recent single- and multicentre studies. Thus, the potential for surgical improvement is likely lower than generally reported when treating patients as part of everyday clinical care.

Postural function in idiopathic normal pressure hydrocephalus before and after shunt surgery: A controlled study using computerized dynamic posturography (EquiTest)

INTRODUCTION Postural dysfunction is one of the major features of idiopathic normal pressure hydrocephalus (iNPH). With computerized dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP. SUBJECTS AND METHODS Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval. RESULTS Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organizing Test (SOT) score in every condition (p=0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients were evaluated three months after shunt surgery and 18/20 (90%) of them were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67%). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions. CONCLUSION CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification

Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49–83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62–89) were examined. 1H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5–3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p=0.02) and lower tNA (p=0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myo-inositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Preoperative and postoperative 1H-MR spectroscopy changes in frontal deep white matter and the thalamus in idiopathic normal pressure hydrocephalus

Background In a previous study we found significantly decreased N-acetyl aspartate (NAA) and total N-acetyl (tNA) groups in the thalamus of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). Objective The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM. Subjects and methods Fourteen patients with iNPH, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of a motor score (MOSs) was performed before and after shunt surgery. Absolute quantitative 1H-MR spectroscopy (1.5 T, volumes of interest 2.5–3 ml) was performed on the patients in the FDWM and in the thalamus, before and 3 months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine, total choline (tCho), myo-inositol (mIns), glutamate and lactate concentrations. MRI volumetric calculations of the lateral ventricles were also performed. Results At 3 months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in the FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between MOS and ventricular reduction was seen. Conclusions Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study

INTRODUCTION Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI). SUBJECTS AND METHODS 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively. RESULTS During daytime the patients took fewer steps (p < 0.001) and their total energy expenditure (TEE) was lower (p < 0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery. CONCLUSION Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report

Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG.

Identical Twins with Idiopathic Normal Pressure Hydrocephalus

Background: The pathogenesis of iNPH is inadequately known. Small vessel disease seems to play an important role but the link to a disturbed CSF dynamic is not described. The familial presentation of idiopathic normal pressure hydrocephalus is extremely rare. Nonetheless, the last years the disclosure of familial occurrence seems to be of interest. The increasing reports on familial iNPH indicate a potential genetic component. Except from iNPH and secondary NPH a third form of NPH, familial NPH, is being widely recognized.

Population based incidence and outcome of surgery for adult patients with hydrocephalus in Sweden

Results 2360 patients were operated on. Mean total incidence of surgery was 5.1±0.9 surgeries/100000/year; 4.7±0.9 shunt surgeries and 0.4±0.1 ETVs. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus the incidence of surgery was 2.2±0.8, 1.9±0.3 and 0.8±0.1 /100000/year respectively. During 2004-2011 the surgical incidence increased in total (p=0.044) and specifically in the age intervals 70-79 years and ≥80 years (p=0.012 and p=0.031). Improvement ≥1 step on the modified Rankin scale (mRS) was seen in 253 of 652 iNPH patients (38.8%) after surgery. Numbers needed to treat was 3.0 for improving one patient from the unfavourable (mRS 3-5) to the favourable (mRS 0-2) group. According to a modified iNPH scale 58% (range 49.3-65.1%, n=704) of the iNPH patients improved. No significant regional differences in incidence, surgical techniques or outcome were found.

O.051 Magnetic Resonance Spectroscopy of INPH-metabolism in the frontal deep white matter and in thalamus

Magnetic Resonance Spectroscopy of INPH -metabolism in the frontal deep white matter and in thalamus