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Magnetic Resonance Spectroscopic Determination of a Neuronal And 1141 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2004.038422 on 16 July 2004. Downloaded from PAPER Magnetic resonance spectroscopic determination of a neuronal and axonal marker in white matter predicts reversibility of deficits in secondary normal pressure hydrocephalus A Shiino, Y Nishida, H Yasuda, M Suzuki, M Matsuda, T Inubushi ............................................................................................................................... J Neurol Neurosurg Psychiatry 2004;75:1141–1148. doi: 10.1136/jnnp.2003.019943 Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. Objective: To investigate whether 1H (proton) magnetic resonance (MR) spectroscopy could predict See end of article for functional outcome in patients after shunting. authors’ affiliations ....................... Methods: Neurological state including Hasegawa’s dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal Correspondence to: shunting. Outcomes were measured postoperatively at one and 12 months and were classified as Dr A Shiino, Department of Neurosurgery, Shiga excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. University of Medical Results: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline Science, Seta, Ohtsu, (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and Shiga 520-2192, Japan; [email protected]. 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, ac.jp and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis Received 30 May 2003 indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive Revised 26 September 2003 value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. Accepted 26 October 2003 Conclusions: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary ....................... NPH, and it would be a useful assessment tool before lumbar drainage. ormal pressure hydrocephalus (NPH) is a chronic preoperative MR spectroscopy could predict outcome in NPH communicating hydrocephalus that presents with the patients who underwent CSF shunting. Ntriad of gait disturbance, cognitive impairment, and urinary incontinence. Patients’ functional status can improve METHODS http://jnnp.bmj.com/ dramatically after ventricular shunt placement, even when Criteria for identifying probable NPH were clinical signs of the cerebrospinal fluid (CSF) pressure is within the normal 1 gait disturbance and either cognitive impairment or urinary range. This pathophysiologically intriguing condition is often incontinence, ventricular enlargement on computed tomo- difficult to differentiate from irreversible brain degeneration. graphy (CT) or MR imaging, and a CSF pressure of less than Among patients diagnosed with idiopathic NPH, shunting is 2 20 mm Hg. Between November 1992 and October 2001 clinically effective in only 30%, while in patients with shunting was carried out at our institution in 49 patients secondary NPH, at least 20–30% of shunts provide little diagnosed with probable NPH. Before shunting, we selected 23 benefit. Despite many clinical studies conducted over the 23 of these patients with no brain lesion such as infarction or on October 2, 2021 by guest. Protected copyright. past three decades, difficulties persist in identifying patients haemorrhage evident on MR imaging or CT. Periventricular with true functional reversibility of NPH on the basis of white matter changes such as periventricular hyperintensity 2 clinical and radiographic criteria. (PVH) or deep white matter hyperintensity (DWMH) were N-acetyl aspartate (NAA) is a metabolite localised almost not considered grounds for exclusion. Two additional 4 exclusively in neurones and their processes and is accepted patients were excluded ultimately because of technical widely as a neuronal marker. Neurones in the central nervous problems. Consequently data from 21 patients were analysed. system have an extremely limited capacity for regeneration, Subjects included eight men and 13 women whose ages and a decrease in NAA has been interpreted as indicating ranged from 38 to 77 years (mean (SD), 62 (10) years). neuronal loss. For example, NAA reduction has been Underlying causes of communicating hydrocephalus observed in patients with vascular dementia such as subcortical arteriosclerotic encephalopathy.56 On the other hand, in NPH, even when cerebral function is impaired by Abbreviations: AIC, Akaike’s information criterion; AID, automatic ventricular enlargement, any neuronal loss should be interaction detection; CBF, cerebral blood flow; Cho, choline minimal; thus the amounts of NAA in the brain should compounds; Cr, creatine; DWMH, deep white matter hyperintensity; remain within the normal range. Magnetic resonance (MR) Gln/Glu, glutamine and glutamate; HDS-R, Hasegawa’s revised dementia scale; mIns, myoinositol; NAA, N-acetyl aspartate; NPH, spectroscopy can be carried out preoperatively to mea- normal pressure hydrocephalus; OEF, oxygen extraction fraction; sure this neuronal marker and thus assess reversibility of PRESS, point resolved, spatially localised spectroscopy; PVH, cerebral dysfunction. In this study we investigated whether periventricular hyperintensity; VOI, volume of interest www.jnnp.com www.jnnp.com 1142 Table 1 Summary of 21 patients undergoing ventriculo-peritoneal shunting Postoperative evaluation Preoperative evaluation (1 month) Postoperative evaluation (1 year) Clinical evaluation Age Period to Gait m- Gait Gait No (years) Sex Aetiology shunt (d) NAA/Cr NAA/Cho Cho/Cr mIns/Cr HDS-R score Incont Rankin HDS-R score Incont m-Rankin HDS-R score Incont m-Rankin 1 month 12 months 1 58 M SAH 16 1.00 0.93 1.08 0.46 00 1 + 5002+ 4022+ 4 Poor Poor 2` 75 F SAH 59 1.59 1.45 1.10 0.19 00 1 + 52332 4 . Excellent – 3 64 M SAH 40 1.67 1.32 1.27 0.22 00 1 + 53042 3002+ 4 Excellent Poor 4 57 M SAH 64 1.72 1.84 0.93 0.28 10 4 + 32252 22942 3 Excellent Excellent 5 62 F SAH 24 1.46 1.36 1.07 0.40 04 1 + 53052 22752 1 Excellent Excellent 6 53 F SAH 46 1.35 1.64 0.83 0.27 05 1 + 52652 22742 1 Excellent Excellent 7 38 M Haemorrhage* 33 1.96 2.39 0.82 0.23 04 1 2 32942 23052 1 Excellent Excellent 8 59 F SAH 24 1.38 1.62 0.85 0.21 00 1 + 51752 23042 1 Fair Excellent 9 77 F SAH 75 1.06 1.19 0.89 0.40 02 1 + 5011+ 5 . Poor (Dead) 10 48 M SAH 45 1.83 1.90 0.96 0.29 04 4 + 32852 23052 1 Excellent Excellent 11 75 F SAH 68 1.25 1.03 1.22 0.45 00 1 + 5073+ 4054+ 3 Fair Fair 12 61 F SAH 50 1.24 1.15 1.08 0.29 00 1 + 5001+ 5001+ 4 Poor Poor 13 57 F SAH 56 1.28 1.26 1.01 0.44 12 1 + 4141+ 4001+ 5 Poor Poor 14 54 M SAH 67 1.51 1.27 1.19 0.16 13 4 2 32352 23052 2 Excellent Excellent 15 50 F Meningitis 11 1.68 1.35 1.25 0.18 14 4 2 32952 2245+ 2 Excellent Fair 16 69 F Tumour` 16 1.97 1.90 1.04 0.38 04 1 + 42852 22852 1 Excellent Excellent 17 65 M Meningitis 49 1.54 1.20 1.29 0.17 07 1 + 52332 4234+ 3 Excellent Fair 18 62 M SAH 76 1.16 0.91 1.27 0.24 00 1 + 5082+ 4113+ 4 Poor Fair 19 74 F SAH 42 1.72 1.35 1.27 0.18 00 1 + 52542 32652 0 Excellent Excellent 20 60 F SAH 42 1.95 1.53 1.27 0.20 00 1 + 42932 32552 0 Excellent Excellent 21 74 F SAH 56 1.40 1.19 1.17 0.20 00 1 + 4241+ 4272+ 4 Fair Fair *Intraventricular haemorrhage of unknown origin. ÀRight acoustic schwannoma, volume ,1cm3. `Patient 2 was lost to follow up at 12 months. Cho, choline compounds; Cr, creatine; F, female; HDS-R, Hasegawa’s dementia scale; incont, incontinence; M, male; mIns, myoinositol; m-Rankin, modified Rankin scale; NAA, N-acetylaspartate; SAH, subarachnoid haemorrhage. Shiino, Nishida, Yasuda, et al J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2004.038422 on 16 July 2004. Downloaded from from Downloaded 2004. July 16 on 10.1136/jnnp.2004.038422 as published first Psychiatry: Neurosurg Neurol J http://jnnp.bmj.com/ on October 2, 2021 by guest. Protected by copyright. by Protected guest. by 2021 2, October on MR spectroscopy in normal pressure hydrocephalus 1143 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2004.038422 on 16 July 2004. Downloaded from http://jnnp.bmj.com/ on October 2, 2021 by guest. Protected copyright. Figure 1 Representative preoperative T2 weighted magnetic resonance (MR) images and MR spectra. The white rectangles indicate the region of interest for MR spectroscopy. Top panel: a patient whose outcome was excellent (case 19). Middle panel: a patient whose outcome was poor (case 9). Bottom panel: a patient whose outcome was poor (case 13). Cho, choline compounds; Cr, creatine; Gln/Glu, glutamine and glutamate; mIns, myoinositol; NAA, N-acetylaspartate. included ruptured cerebral aneurysm in 14 patients, subar- and increased duration of spontaneous eye opening were also achnoid haemorrhage of unknown origin in three, brain considered to represent improvement. A low pressure valve tumour in one, meningitis in two, and intraventricular was used for the ventriculo-peritoneal shunt, and function of haemorrhage in one. Patients with idiopathic NPH were not the shunt system was monitored closely.
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