Klein details recent major advancements in the genetics of parkinsonism and outlines the major challenges for the future. These include the definition of the phenotypic and genotypic spectrum of the monogenic forms, a revised terminology and classification of parkinsonian syndromes, identification of genetic susceptibility factors, and development of guidelines for genetic testing and of new treatment for Parkinson disease. She provides an authoritative and compelling discussion of the new genetics and genomics of this major area of movement disorders.
Henson describes the recent impressive therapeutic advance provided by temozolomide over conventional therapies for glioblastoma multiforme (Figure). He considers thoughtfully the clinical problem of glioblastoma multiforme, discusses the details of the positive phase 3 clinical trial, and examines the results of the translational study of methylguanine methyltransferase gene silencing. He cites a welcome new problem in neuro-oncology, that is, the impact of a new treatment standard on existing and future clinical trials.
Overall survival curves from the phase 3 trial (A). The survival curves for patients treated with temozolomide whose tumors did or did not have methylguanine methyltransferase (MGMT) gene silencing (B).
Rippon and colleagues report their findings to further delineate the frequency, nature, and implications of cognitive impairment in amyotrophic lateral sclerosis and to assess previously identified risk factors. They found that a third of the patients in their series showed evidence of cognitive impairment in a pattern consistent with that reported in frontotemporal lobar dementia. Michael J. Strong, MD, FRCPC, provides a thoughtful and measured editorial perspective.
Josephs et al describe their experience with the condition they term benign tremulous parkinsonism. They define it as a distinctive clinical entity characterized by tremor predominance, including postural and sometimes kinetic hand tremor, plus minimal progression of other aspects of parkinsonism despite at least 8 years of disease duration. The tremor is often not very responsive to levodopa therapy, and most patients in their series had immediate family members with a diagnosis of tremor or parkinsonism. Padraig E. O’Suilleabhain, MD, gives his views on these clinical issues in a well-focused editorial.
Establishing a very insightful and useful perspective, de Lau and colleagues provide a study showing the earliest subjective patient complaints that precede and are indicators that predict the subsequent onset of Parkinson disease. Patients who reported stiffness, tremors, or imbalance at baseline, even when standard neurological testing cannot yet demonstrate any motor symptoms, had a significantly increased risk to develop Parkinson disease during the follow-up period.
Leverenz et al studied the clinical and neuropathologic variability of Lewy body pathology (LBP) in a large number of familial Alzheimer disease cases with mutations in 2 presenilin (PSEN) genes. Of note, they found that the amygdala was the most vulnerable site for LBP. Virtually all of the PSEN1 mutation cases had LBP in the amygdala (96%). PSEN1 mutation cases also had more frequent LBP in the amygdala and neocortex than those with a PSEN2 mutation. Even within families with a single mutation of either PSEN1 or PSEN2, there was frequent variability of the LBP. Thus, there are important genetic influences on the presence of LBP in familial Alzheimer disease as demonstrated by the differences between PSEN1 and PSEN2 mutation cases. These findings will be of considerable value in defining the cellular basis of behavioral features, including psychotic features, encountered in familial Alzheimer disease cases with LBP.
Gaig and colleagues determined the frequency of the LRRK2 G2019S and R1441G mutations in Spanish patients with Parkinson disease and characterized their family history and clinical features. They report that the G2019S mutation frequency in patients with Parkinson disease in northeast Spain is similar to that in other reported European regions. The R1441G mutation is very uncommon in this region.
Keane reports that seeing triple is not necessarily a sign of hysteria. Of 13 440 patients, 13 patients in his series reported seeing objects in triplicate. Eleven of 13 patients had eye movement abnormalities. Eight of 13 appeared to have oscillopsia or binocular diplopia whereas the remainder (5 of 13) exhibited monocular diplopia or triplopia, with or without ocular motor abnormalities, as a functional complaint.
Pittock and colleagues provide important findings concerning magnetic resonance imaging abnormalities seen in patients with neuromyelitis optica (NMO). Sixty patients fulfilled their criteria of NMO and brain magnetic resonance imaging lesions were detected in 36 patients (60%). Neuromyelitis optica–IgG was detected in 41 patients (68%). Several had magnetic resonance imaging lesions similar to those seen in patients with multiple sclerosis. Of note, they conclude that asymptomatic brain lesions are not uncommon in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These significant findings justify revision of diagnostic criteria for NMO to allow for brain involvement.
Gøransson et al report their findings establishing small-diameter nerve fiber neuropathy in patients with systemic lupus erythematosus. They found that the mean ± SD density of the intraepidermal small-diameter nerve fibers in patients with systemic lupus erythematosus was 7.5 ± 3.8 fibers per millimeter. Eight patients (13%) had densities below reference values consistent with small-diameter nerve fiber neuropathy, and nerve conduction study results were normal in 6 of them. Eleven patients (18%) had an abnormal nerve conduction study result reflecting large-diameter nerve fiber neuropathy. Their findings add considerable new data that show that a pure small-diameter nerve fiber neuropathy occurs in systemic lupus erythematosus.
Fitzgerald and colleagues identified 42 children with neonatal sinovenous thrombosis. They identified a broad differential diagnosis, but the specific cause can be difficult to define. Treatment beyond supportive care is rarely employed and outcomes can be severe.
Bergamaschi et al studied 22 patients with congenital adrenal hyperplasia and 10 (45%) showed significant white matter abnormalities on magnetic resonance imaging. They found that congenital adrenal hyperplasia is frequently associated with subclinical brain white matter involvement. The diagnosis of congenital adrenal hyperplasia should be suspected in young subjects with brain magnetic resonance imaging white matter abnormalities.
Scheid and colleagues studied the extent and severity of diffuse axonal injury–associated cognitive impairment by the use of magnetic resonance imaging and detailed neuropsychological testing. Pure diffuse axonal injury was defined by the findings of traumatic microbleeds on T2-weighted gradient-echo images. All patients showed impairments of 1 or more cognitive subfunctions, and no cognitive domain was spared. Memory and executive dysfunctions were most frequently encountered. They concluded that a magnetic resonance image lesion pattern compatible with isolated diffuse axonal injury is commonly associated with persistent cognitive impairment.
Fernández et al used magnetoencephalographic recordings as predictors of risk of developing Alzheimer disease in patients with mild cognitive impairment. They report that left parietal δ dipole density permitted a reliable classification of patients with Alzheimer disease and mild cognitive impairment. The estimated relative risk of conversion to Alzheimer disease was increased by 350% in those patients with mild cognitive impairment with high scores on left parietal δ dipole density. A magnetoencephalography-based assessment of patients with Alzheimer disease and mild cognitive impairment might be a useful clinical test in the future.
Murrell and colleagues studied the effect of apolipoprotein E on the risk of Alzheimer disease in African American patients. Of note, they found that apolipoprotein E ε4 was significantly associated with an increased risk for Alzheimer disease and that apolipoprotein E ε2 had a protective effect.
Geda et al report that cognitively normal elderly individuals who develop depression are at increased risk of subsequent mild cognitive impairment. They also found a synergistic interaction between depression and apolipoprotein E genotype.
Colosimo and colleagues show that primary and secondary hemifacial spasm share a number of demographic and clinical features. The 2 forms differ in clinical presentation, and synkinesis is present in a significant proportion in both types of hemifacial spasm.
This Month in Archives of Neurology. Arch Neurol. 2006;63(3):315-317. doi:10.1001/archneur.63.3.315