Three cases of CLIPPERS: a serial clinical,laboratory and MRI follow-up study

The aim of the study was to further determine the pathophysiology, clinical course, MRI-features and response to therapy of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), which has recently been proposed as a rare chronic inflammatory central nervous system disorder responsive to immunosuppressive therapy. Three patients with this rare entity underwent serial clinical and bimonthly MRI follow-up over a period of up to 16 months. Extensive laboratory work-up and brain biopsy were performed. Intravenous methylprednisolone or oral dexamethasone was administered as treatment, additionally cyclophosphamide in one patient. Clinically, diplopia, nystagmus, ataxia and facial paresthesia were the cardinal symptoms. Magnetic resonance imaging (MRI) disclosed patchy spot-like gadolinium enhancement in a “salt-and-pepper like appearance” in the pons, midbrain and cerebellum, in two cases with thalamic and in the other with spinal involvement. Brain biopsies demonstrated a predominantly angiocentric but also diffuse infiltration pattern by small mature lymphocytes. Treatment with steroids led to rapid clinical improvement and marked resolution of MRI lesions. As discontinuation of steroids led to clinical relapse, one patient was treated with a further course of steroids and the other with steroids and cyclophosphamide as immunosuppressive therapy. This led to stable remission with only mild clinical residue and normalization of MRI. Extensive laboratory and radiological work-up could not identify any other cause of the disease. Of note, in two cases a marked elevation of IgE in serum was found initially and throughout the course. CLIPPERS seems to be a distinct inflammatory central nervous system disorder. It shows characteristic MRI core features. Extrapontine involvement seems to be frequent. Histologically it is characterised by predominantly angiocentric infiltration by small mature lymphocytes. A pathogenetic relationship between the elevated IgE levels and the perivascular infiltrates can be presumed. It is responsive to immunosuppressive therapy and can require prolonged or maintenance treatment.     

主要累及全脊髓和脑干的CLIPPERS一例

目的探讨类固醇激素反应性慢性淋巴细胞性炎性反应伴脑桥血管周围强化症(CLIPPERS)的临床表现、影像学及病理改变,探讨其可能的发病机制。方法对1例主要累及全脊髓及脑干的CLIPPERS患者临床资料及影像学进行分析,并结合文献复习此病的特征表现及鉴别诊断。结果本例男性29岁,进行性双下肢无力、共济失调2年、及伴腹部麻木1年余。头颅磁共振(MRI)增强扫描示脑干、全脊髓多发小斑片状异常强化信号,边界较清楚,呈"胡椒粉征"。病变分布较均匀,延髓及脊髓分布更密集。另外双侧丘脑、基底核、小脑半球见散在类似异常强化灶。软脑膜及软脊膜也可见多处轻度线样强化。经糖皮质激素治疗2个月后,患者临床症状明显减轻。复查MRI示上述异常强化灶大部分消失,残存病灶缩小且强化程度减轻,边界变模糊。影像学提示病变明显好转。结论在有些CLIPPERS患者,MRI的强化灶主要累及脑干、脊髓全长及软脑(脊)膜,不一定以脑桥为中心。CLIPPERS糖皮质激素治疗效果好。CLIPPERS的诊断应结合临床、影像学及实验室检查,必要时行脑组织活检。     

Proton magnetic resonance spectroscopy study of bilateral thalamus in juvenile myoclonic epilepsy.

PURPOSE: To investigate neuronal dysfunction in the thalami of juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 15 consecutive patients (10 women, 5 men) with JME (mean age 20.3 years) and 16 healthy volunteers (10 women, 6 men) (mean age 24.5 years). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical electroencephalogram (EEG) of JME and normal magnetic resonance imaging (MRI). We determined N-acetylaspartate (NAA) values and NAA over creatine-phosphocreatine (Cr) values. Mann-Whitney U-test was used to evaluate group differences. RESULTS: Group analysis showed that echo time (TE) 270 integral value of NAA over left thalamus were significantly decreased in JME patients as compared with controls (34.6033+/-15.8386; 48.0362+/-22.2407, respectively, P=0.019). Also group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (right side, 2.21+/-1.07; left side 2.00+/-0.72) as compared with controls (right side, 3.45+/-1.50; left side, 3.08+/-1.60; P=0.011 and P=0.030, respectively). CONCLUSION: In the previous studies, NAA values in patients with JME found that they were not statistically lower in thalami than control group. But, in our study, NAA value was found low as well. It has been known that NAA is a neuronal marker and hence it is a valuable metabolite in the neuron physiopathology. As a result, in the patients with JME we tried to support the theory that the underlying mechanism of the generalized seizures was the abnormal thalamocortical circuity, determining the thalamic neuronal dysfunction in MRS statistically.     

Thalamic dysfunction in juvenile myoclonic epilepsy: a proton MRS study

PURPOSE: To investigate neuronal dysfunction in the thalami of patients with juvenile myoclonic epilepsy (JME) by using proton magnetic resonance spectroscopy (MRS). METHODS: We performed single-voxel proton MRS over the right and the left thalami of 10 consecutive patients (five women) with JME (mean age, 31.6 years) and 10 age-matched healthy volunteers (five men). All patients had seizure onset in late childhood-teenage, normal neurologic examination, typical EEG of JME, and normal high-resolution MR imaging (MRI). We determined ratios of N-acetylaspartate (NAA) over creatine-phosphocreatine (Cr). Values <2 standard deviations from controls were considered abnormal. We performed analysis of variance to evaluate group differences. RESULTS: Group analysis showed that thalami NAA/Cr ratios were significantly decreased in JME patients (left side, 1.58 +/- 0.26; right side, 1.5 +/- 0.15) as compared with controls (left side, 1.98 +/- 0.18; right side, 1.88 +/- 0.15; p = 0.001 and p = 0.007, respectively). Individual analysis showed that nine of the 10 patients had abnormal NAA/Cr in at least one of the thalami. CONCLUSIONS: This study shows evidence of neuronal dysfunction in the thalami of patients with JME, which may have relevance for the mechanisms of seizure generation in this form of generalized epilepsy.     

颅内间变型星形细胞瘤影像表现回顾性分析

目的 分析间变型星形细胞瘤的螺旋CT和磁共振影像表现,以提高对本病的认识.方法 回顾性分析颅内间变性星形细胞瘤螺旋CT和磁共振影像表现,使用GE64排螺旋CT和GE 3.0T磁共振,所有病例均进行CT平扫+增强扫描和磁共振SE序列T1WI和T2WI、DWI、MRS、FLAIR序列及对比增强T1WI扫描.结果 间变型星形细胞瘤在螺旋CT和磁共振扫描时密度或信号多不均匀,增强后可见不规则斑片样强化,占位效应明显.MRS显示病灶Cho/NAA的比值5.5～6.3,Cho/Cr比值4.7～5.3.结论 间变型星形细胞瘤的CT及MRI表现具有一定的特征性,螺旋CT和磁共振影像学检查有助于间变型星形细胞瘤的诊断和鉴别诊断.     

Thalamic proton magnetic resonance spectroscopy in vegetative state induced by traumatic brain injury

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (MRS), a newer radiographic technology, would be useful in the evaluation of the thalamus of patients in vegetative states resulting from traumatic brain injury. METHODS: 14 victims of severe traumatic brain injury who were in the vegetative state and whose magnetic resonance images of the thalamus were normal underwent bilateral thalamic proton (MRS) studies. The N-acetyl aspartate to creatine (NAA:Cr) and choline to creatine (Cho:Cr) ratios were obtained for each patient. The proton thalamic MRS findings of patients who were in a persistent vegetative state (n = 8) and in patients who had regained awareness after being in the vegetative state (n = 6) were compared with proton thalamic MRS findings in five healthy volunteers. RESULTS: While conventional magnetic resonance imaging suggested that each patient had a normal thalamus, proton MRS indicated that the thalamus of each patient in the series was damaged. The NAA:Cr ratio was significantly lower in the thalami of both the patients who remained in a persistent vegetative state for the duration of the study and in those who regained awareness after being in the vegetative state (p < 0.001). In addition, NAA:Cr ratios were lower in the group of patients who remained in a persistent vegetative state than in the group of patients who regained awareness after being in the vegetative state (p < 0.001). CONCLUSIONS: Results suggest that the NAA:Cr ratio within the thalamus is significant and that thalamic MRS may be helpful when attempting to determine the degree of severity of neuronal and axonal injury in patients in the vegetative state.     

Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus,thalamus, and prefrontal cortex

Single voxel proton magnetic resonance spectroscopy (1H MRS) was used to study the metabolites N-acetylaspartate (NAA), choline (CHO), and myo-inositol (ml) in order to test a neurodegenerative hypothesis in schizophrenia (decrease of NAA, increase of CHO, and increase of ml) and a cerebral asymmetry of these metabolites. 1H MRS was performed in 17 schizophrenia patients and 14 healthy subjects in three cerebral areas highly involved in the pathophysiology of schizophrenia (the prefrontal cortex, the thalamus, and the hippocampus). The ratio amplitudes between metabolites and creatine plus phosphocreatine (Cr) were determined. No difference in the metabolites existed between patients and healthy subjects. However, relationships were noted between NAA/Cr and age in the thalami of the schizophrenia patients (r = -0.37; p = 0.14) and healthy subjects (r = -0.52; p = 0.05). A significant correlation was observed between NAA/Cr and age of onset of illness in the hippocampi of schizophrenia patients (r = -0.59; p < 0.05). Moreover, NAA/Cr was lower in the right than in the left prefrontal cortex in both schizophrenia patients and healthy subjects. There was no relationship between the metabolites and duration of illness or dose of antipsychotics. These findings might suggest a neurodegenerative process in the hippocampi of schizophrenia patients with late onset of illness, and the NAA/Cr ratio could be a marker of aging in the thalami.     

Long-term Outcomes of CLIPPERS (Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids) in a Consecutive Series of 12 Patients

BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE To describe the disease course of CLIPPERS. DESIGN A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING Academic research. PATIENTS Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES The therapeutic management of CLIPPERS was evaluated. RESULTS Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.     

Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.     

脑干胶质瘤磁共振波谱分析

目的探讨磁共振波谱(Magnetic resonance spectroscopy,MRS)在脑干胶质瘤诊断中的意义。方法回顾性分析10例脑干胶质瘤的临床资料,肿瘤位于中脑1例,中脑脑桥1例,脑桥7例,延髓1例。均行MRS检查,对肿瘤区、肿瘤边缘区和正常对照区进行对照研究。结果MRS均显示肿瘤区N-乙酰天门冬氨酸(N-acetylaspartate,NAA)峰值下降,胆碱(Choline,Cho)峰上升。与肿瘤边缘区和正常对照区比较,肿瘤区NAA/Cr明显减低,Cho/Cr和Cho/NAA明显升高。星形细胞瘤4例,间变性星形细胞瘤1例,胶质母细胞瘤2例;另3例根据临床特点和影像学表现诊断为脑干胶质瘤。结论MRS可检测到脑干胶质瘤的代谢改变,具有无创、敏感、诊断准确的特点。     

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.     

Magnetic resonance spectroscopy of the thalamus in patients with typical absence epilepsy.

PURPOSE: To investigate possible neuronal dysfunction of the thalamus in patients suffering from typical absence epilepsy, using magnetic resonance spectroscopy (MRS). Special attention was paid to levels of N-acetylaspartate (NAA) and creatine (Cr), and to the NAA/Cr ratio. METHODS: MRS was performed over the right and left thalamus in nine patients suffering from typical absence epilepsy, and in nine sex- and age-matched healthy controls. All patients and controls were examined using a standard MRS-CSI (chemical shift imaging) technique. RESULTS: Statistical analysis of the obtained data demonstrated a significantly lower thalamic NAA/Cr ratio in patients with typical absence epilepsy when compared to the healthy controls. Our MRS data showed symmetrical distribution of NAA/Cr ratio in the right and left thalamus within both the patient group and the group of healthy controls. No significant correlation between the patients' thalamic NAA/Cr values and the duration of the epilepsy or seizure frequency was revealed. CONCLUSIONS: The present MRS data clearly indicate neuronal dysfunction in the thalami of patients with typical absence epilepsy. In agreement with other recent MRS findings in different idiopathic generalized epilepsy syndromes, our results confirm the role of the thalamus as an important structure in the pathogenesis of typical absence epilepsy.     

MRS Findings in Cerebral Coenurosis due to Taenia Multiceps

Cerebral coenurosis due to Taenia multiceps is a rare infection with no case reports from India. A 55‐year‐old male patient had presented with progressive symptoms of hemiparesis of 1‐year duration. Magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) of the lesion was performed that showed a septated cystic lesion in left parieto‐occipital lobe. Multivoxel MRS through the lesion was performed using repetition time of 1500 ms and time to echo of 144 ms at 3T MRI. MRS showed mildly elevated choline (Cho), depressed creatine (Cr), and N‐acetyl aspartate (NAA), a large peak of lactate, pyruvate, and acetate peaks. To best of our knowledge, there has been no reported case of in vivo proton MRS finding ever reported. We present MRS findings in this operatively proven case of T. multiceps cyst of the brain.     

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.     

原发性侧索硬化的临床和影像学特征

目的 探讨胀发性侧索硬化（PLS）的临床和影像学特征。方法 对3例PLS患者的临床和影像学资料进行分析。结果 本组PLS患者女2例、男1例,均为缓慢起病。其中例1首发症状为右上肢僵硬、无力,例2为两下肢僵硬、无力,例3表观为假性延髓麻痹,随病情的进展,均出现四肢痉挛性瘫痪,肌力Ⅲ～Ⅳ级,肌张力呈折刀样增高,四肢腱反射亢进,两侧踝阵孪及Babinski征（＋）,头颅MRI T2 WI可见两侧内囊、大脑脚、运动区皮质及腑桥丛底部有异常高信号,^1H磁共振波谱（^1HMRS）示在病灶区有乙酰天门冬氨酸盐（NAA）降低及NAA／肌酸（Cr）比值降低。结论 PLS的临床症状、体征和MRI有特征性改变,^1HMRS的改变也有助于诊断。     

<Superscript>1</Superscript>H MR spectroscopy of gray and white matter in carbon monoxide poisoning

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. ¹H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1–6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N-acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by ¹H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed.     

MR spectroscopy in monitoring the treatment of Wilson's disease patients

The aim of this study was to determine the effectiveness of brain proton magnetic resonance spectroscopy (¹H‐MRS) for monitoring therapy in Wilson's disease (WD) patients. Voxels were located in the globus pallidus (right, left). We followed 17 newly diagnosed WD cases for 1‐year period. During this observation period, 6 neurological and 9 hepatic patients improved, while 2 neurological patients deteriorated. The pretreatment ¹H‐MRS analysis showed a statistically significant lower level of mI/Cr, NAA/Cr, and higher Lip/Cr in all WD patients with improvement compared with controls. In patients with hepatic signs, a statistically significant increase of mI/Cr and Glx/Cr was observed in the second (1 year posttreatment) ¹H‐MRS. In patients with neurological improvement after treatment in the follow‐up ¹H‐MRS, a statistically significant increase of NAA/Cr was noted. During neurological deterioration, a decrease of Glx/Cr and NAA/Cr was seen, in contrast to another neurologically impaired patient with liver failure exacerbation, where a decrease of mI/Cr and increase of Glx/Cr was observed. The alternations of NAA/Cr ratio in neurologically impaired patients and mI/Cr and Glx/Cr in patients with liver failure could be a sensitive marker of the clinical recovery and deterioration in those WD patients. ¹H‐MRS is a technique that can be used for accurate monitoring of treatment efficacy in WD patients. © 2008 Movement Disorder Society     

Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report

A novel type of encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 and few additional patients were reported since then. Partially due to its unknown aetiology and a lack of pathognomonic features some have suggested that CLIPPERS may not represent a distinct disease, but rather a syndrome with different underlying aetiologies. Here we report a 49-year-old German female who presented with a number of clinical and paraclinical features described as typical for CLIPPERS, while additionally showing symptoms and findings compatible with primary angiitis of the CNS (PACNS). This case may establish a previously unnoted link between two poorly understood autoimmune conditions of the CNS.     

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different.     

Intact presupplementary motor area function in early,untreated Parkinson's disease

Although motor symptoms of Parkinson's disease (PD) are initially responsive to dopamine replacement therapy, nonresponsive features develop over time, suggesting that impaired dopaminergic function alone may not be wholly responsible for all the motor features of the disease. Previous studies suggest impaired function in the presupplementary motor area (pre‐SMA) in PD. Our objective was to determine whether pre‐SMA abnormalities are present in untreated patients with early disease. We measured N‐acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in pre‐SMA in 26 untreated patients with early PD (disease duration 3.0 ± 2.0 yr) and 15 control subjects with single voxel magnetic resonance spectroscopy. Neither NAA/Cr nor Cho/Cr ratios differed significantly between groups. These observations suggest that, although pre‐SMA function is impaired in moderately advanced PD, it is relatively spared in early disease. We suggest that pre‐SMA dysfunction is in part responsible for the dopamine nonresponsive features associated with disease progression. © 2008 Movement Disorder Society