Long-standing Deficits Research Articles

Polyclonal IgM influence oligodendrocyte precursor cells in mixed glial cell cultures: implications for remyelination

Polyclonal immunoglobulins for intravenous use (IVIg) are a potent immunomodulator and have been shown to be effective in several immune-mediated diseases. This includes inflammatory demyelinating diseases of the central nervous system (CNS) like multiple sclerosis (MS). Besides their immunomodulatory function, IVIg have been proposed to enhance remyelination based on studies in the animal model of Theiler's murine encephalomyelitis virus (TMEV). Disappointingly, recent treatment trials in patients with MS have failed to demonstrate repair of longstanding deficits. Since the clinical trials have used IVIg that contained nearly exclusively IgG, whereas the most pronounced effect in TMEV was seen with IgM, this could be a possible explanation for the negative outcome in the MS trials. Here we have examined the effects of a new polyclonal IgM preparation (IVIgM) on cultured oligodendrocyte precursor cells (OPCs). To achieve successful remyelination, OPCs proliferate, migrate, and differentiate into mature myelinating oligodendrocytes. IVIgM and commercial IVIg preparations had no influence on proliferation and differentiation of either isolated OPCs or OPCs in coculture with microglia. In contrast, IVIgM inhibited the proliferation of OPCs in mixed glial cultures containing astrocytes and microglia. This was not seen in cultures treated with IVIg, albumin, or interferon-γ (IFN-γ), suggesting that this is a specific effect of IVIgM. Differentiation was slightly delayed by IVIgM in mixed glial cultures, but this was not statistically significant and interferon-γ had a similar effect. These results underline the importance of IgM in influencing OPCs and corroborate the in vivo findings that polyclonal IgM are more potent than IgG in their capacity to influence remyelination. The exact mechanism of how this modulation of OPCs is achieved remains unknown, but a complex interaction among all cells present in the CNS has to be postulated.

Narcissism in the Epistemological Pit

For some people, the move from dualistic to relativistic epistemological thought is accompanied by significant psychological distress. Although there are several possible sources of psychological difficulty in stage transition, we argue that long-standing deficits in object relations can predispose a person to clinical crisis during particular life phase and cognitive stage transitions. Specifically, a person is likely to experience clinical crisis during a particular life phase or stage transition if that developmental advance requires abandoning strategies that have been used to shore up faulty self and object representations. The life phase move from adolescence to adulthood and the cognitive stage shift from dualistic to relativistic thought often pose particular difficulty for persons with a narcissistic personality organization. The epistemological move to relativism can be particularly traumatic when adolescents have cathected their own intellectual products (ideas, ideologies) as idealized self-objects. A case study is presented to illustrate the clinical crisis that can be precipitated by the narcissistic adolescent's loss of intrapsychic supports in the move to adulthood and to committed relativism.

The Long-term Effects of Unilateral Lower Limb Musculoskeletal Injury on Bone Mineral Density and Isometric Quadriceps Strength

Summary Musculoskeletal injuries of the lower limb are commonplace and can lead to long-standing deficits in bone mineral density (BMD) and muscle strength. This may predispose subjects to re-injury and lower their threshold for functional ability. This study aims to investigate the relationship between BMD and peak isometric quadriceps strength and considers whether subsequent strength training is of benefit. Ten subjects (two female) with previous lower limb musculoskeletal injuries were assessed. The BMD in the knee region was measured bilaterally using dual energy X-ray absorptometry (DEXA, model DPX-L). The peak isometric quadriceps strength was assessed using the KinCom 500H isokinetic dynamometer. The injured limb was compared to the uninjured limb (I/UI%). Significant differences were seen between the injured and uninjured limb for BMD in the femur (p = 0.039), tibia (p = 0.014) and in the combined site (p = 0.017); and peak isometric quadriceps strength (p > 0.001). No relationship was found between the decrements in muscle strength and BMD. A further pilot study (n = 6) was conducted to assess the impact of a 12-week home exercise training programme on the BMD and isometric quadriceps strength deficits. These results were encouraging with increases in the quadriceps strength and/or BMD and a statistically significant increase in the load lifted in training.

Prognosis in nonconvulsive status epilepticus

ABSTRACT Determining the prognosis in nonconvulsive status epilepticus (NCSE) is complicated by several factors: under‐recognition of NCSE with its spontaneous resolution (thus decreasing the “denominator” of total cases that will have a poor outcome); incorrect diagnosis of NCSE based on misinterpretation of EEG “epileptiform” activity; mis‐classification of certain EEG patterns as NCSE ( e.g. PLEDs; triphasic waves); and grouping of different populations that have markedly different co‐morbidities (ambulatory patients with NCSE together with comatose patients with electrographic seizure activity on EEG). There are almost no prospective studies with premorbid neuropsychometric studies, and retrospective studies typically include isolated cases, or case series that include conditions in which the cause of NCSE itself causes cognitive morbidity. To summarize available data, absence status (ambulatory generalized non‐convulsive status epilepticus) would appear to carry no lasting morbidity. Complex partial status epilepticus in ambulatory patients rarely results in measurable permanent neurologic deficit, although rarely, short or longstanding deficits may clearly occur. Because intensive treatment with intravenous anticonvulsants ( e.g. benzodiazepines or phenytoin) can confer morbidity, the equation has not yet been made as to whether the morbidity of such intensive treatment for all cases of NCSE exceeds the morbidity of the disease itself. Larger, prospective studies will be needed to truly determine the prognosis in the different types of NCSE, stratified according to associated degrees of impairment (minimally impaired, moderately obtunded, comatose).

Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia.

To report neuropsychologic functions and developmental problems of patients with congenital nonprogressive cerebellar ataxia. Growing interest in cerebellar function has prompted closer attention to cognitive impairments in patients with cerebellar damage. The authors studied 11 patients with nonprogressive congenital ataxia (NPCA) with Wechsler's intelligence testing, with additional tests of attention, memory, language, visual perception, and frontal functions. Seven of the 11 patients had an IQ of 60 to 92, with marked nonverbal deficits and subnormal to normal verbal performance (group A). Four patients had an IQ of 30 to 49 without pronounced profile asymmetry (group B). Four of the 7 group A patients had decreased alertness and sustained attention, but all had normal selective attention. Tests of frontal functions and memory yielded higher verbal scores than nonverbal scores. There was no deficit on the Aachener Naming Test (similar to the Boston Naming Test), because there were marked difficulties in the majority with visuoconstructive tasks and visual perception. Group B was significantly abnormal in almost all subtests, having a less prominent but similar profile. Patients with NPCA have significant cognitive deficits with an asymmetric profile and better verbal than nonverbal performance. Effects on nonverbal performance of longstanding deficits in visuospatial input during learning, the influence of impaired procedural learning, and asymmetric plasticity of the cerebral hemispheres may contribute to this uneven neuropsychological profile.

Congenital vertebral displacement.

We defined congenital vertebral displacement as displacement at a single vertebral level that results in an abrupt displacement of the neural canal. We reviewed the data on 642 patients who had congenital vertebral abnormalities and identified ten who had congenital vertebral displacement. There were two patterns of deformity: Type A (eight patients) consisted of displacement in the sagittal plane only, and Type B (two patients), rotatory, transverse, and sagittal displacement. The spinal deformity was usually noted in infancy. Neurological deficits were identified at the time of presentation or developed later in six patients. Two patients had a sudden onset of paraplegia after slight trauma, two had a gradual onset of neurological abnormalities, and two had neurological abnormalities when they were first seen. Three patients had congenital anomalies of the spinal cord. We found marked mechanical instability intraoperatively in five patients, and we believe that the instability in combination with compression of the spinal cord resulted in myelopathy. We recommend combined anterior and posterior arthrodesis of the spine for the treatment of this disorder. We believe that decompression of the spinal cord is indicated for patients who have a neurological deficit of recent onset or a progressive neurological deficit. Decompression of the spinal cord may also be indicated for the treatment of long-standing deficits after spinal stability has been obtained.

Perpetual retraining in an adult cerebral palsy patient: A case of a deficit in cross-modal equivalence

Abstract A 23-year-old cerebral palsy patient with multiple perceptual-motor impairments was found, on testing, to have a severe deficiency in cross-modal transfer, which could account for many of these impairments. A training program to improve performance on cross-modal transfer problems was designed based on Gibson's developmental model of perceptual learning. The training was carried out over a one-year period. The patient's performance improved on cross-modal tasks as well as on perceptual-motor tasks for which there had been no specific training. This study indicates that even long-standing neuropsychological deficits are amenable to training.