Andrea Orioli

Noninvasive Spinal Cord Stimulation: Technical Aspects and Therapeutic Applications.

Electrical and magnetic trans‐spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico‐spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord.

Descending motor pathways and cortical physiology after spinal cord injury assessed by transcranial magnetic stimulation: a systematic review

We performed here a systematic review of the studies using transcranial magnetic stimulation (TMS) as a research and clinical tool in patients with spinal cord injury (SCI). Motor evoked potentials (MEPs) elicited by TMS represent a highly accurate diagnostic test that can supplement clinical examination and neuroimaging findings in the assessment of SCI functional level. MEPs allows to monitor the changes in motor function and evaluate the effects of the different therapeutic approaches. Moreover, TMS represents a useful non-invasive approach for studying cortical physiology, and may be helpful in elucidating the pathophysiological mechanisms of brain reorganization after SCI. Measures of motor cortex reactivity, e.g., the short interval intracortical inhibition and the cortical silent period, seem to point to an increased cortical excitability. However, the results of TMS studies are sometimes contradictory or divergent, and should be replicated in a larger sample of subjects. Understanding the functional changes at brain level and defining their effects on clinical outcome is of crucial importance for development of evidence-based rehabilitation therapy. TMS techniques may help in identifying neurophysiological biomarkers that can reliably assess the extent of neural damage, elucidate the mechanisms of neural repair, predict clinical outcome, and identify therapeutic targets. Some researchers have begun to therapeutically use repetitive TMS (rTMS) in patients with SCI. Initial studies revealed that rTMS can induce acute and short duration beneficial effects especially on spasticity and neuropathic pain, but the evidence is to date still very preliminary and well-designed clinical trials are warranted. This article is part of a Special Issue entitled SI: Spinal cord injury.

Spinal cord injury affects I-wave facilitation in human motor cortex

Transcranial magnetic stimulation (TMS) is a useful non-invasive approach for studying cortical physiology. To further clarify the mechanisms of cortical reorganization after spinal cord injury (SCI), we used a non-invasive paired TMS protocol for the investigation of the corticospinal I-waves, the so-called I-wave facilitation, in eight patients with cervical SCI. We found that the pattern of I-wave facilitation significantly differs between SCI patients with normal and abnormal central motor conduction (CMCT), and healthy controls. The group with normal CMCT showed increased I-wave facilitation, while the group with abnormal CMCT showed lower I-wave facilitation compared to a control group. The facilitatory I-wave interaction occurs at the level of the motor cortex, and the mechanisms responsible for the production of I-waves are under control of GABA-related inhibition. Therefore, the findings of our small sample preliminary study provide further physiological evidence of increased motor cortical excitability in patients with preserved corticospinal projections. This is possibly due to decreased GABAergic intracortical inhibition. The excitability of networks producing short-interval intracortical facilitation could increase after SCI as a mechanism to enhance activation of residual corticospinal tract pathways and thus compensate for the impaired ability of the motor cortex to generate appropriate voluntary movements. Finally, the I-wave facilitation technique could be used in clinical neurorehabilitation as an additional method of assessing and monitoring function in SCI.

rTMS modulates reciprocal inhibition in patients with traumatic spinal cord injury

Study design:Randomized, double-blind, crossover, sham-controlled trial.Objectives:Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) leads to a significant reduction of spasticity in subjects with spinal cord injury (SCI), but the physiological basis of this effect is still not well understood. The purpose of this study was to evaluate the disynaptic reciprocal Ia inhibition of soleus motoneurons in SCI patients.Setting:Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical University, Salzburg, Austria.Methods:Nine subjects with incomplete cervical or thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over the contralateral M1. We compared the reciprocal inhibition, the Modified Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at baseline, after the last session and 1 week later in the real rTMS and sham stimulation groups.Results:We found that real rTMS significantly reduced lower limb spasticity and restored the impaired excitability in the disynaptic reciprocal inhibitory pathway.Conclusions:In a small proof-of-concept study, rTMS strengthened descending projections between the motor cortex and inhibitory spinal interneuronal circuits. This reversed a defect in reciprocal inhibition after SCI, and reduced leg spasticity.

Impaired cholinergic transmission in patients with Parkinson's disease and olfactory dysfunction

Olfactory dysfunction represents a frequent and disturbing non-motor manifestation of Parkinsons disease (PD). The pathophysiology of olfactory dysfunction in PD is still poorly understood. Experimental evidence suggests that olfactory impairment could be related to central cholinergic dysfunction. Short latency afferent inhibition (SAI) technique gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with different degrees of olfactory dysfunction. We applied SAI technique in 31 patients with PD. These patients also underwent Olfactory Event-Related Potentials (OERPs) studies to objectively evaluate the olfactory system and a battery of neuropsychological tests to assess the cognitive functions. Absent OERPs indicated a severe olfactory dysfunction in 13 subjects. The presence of OERPs with an alteration in latency and/or amplitude can be considered as a borderline condition of slight alteration of smell and was found in other 15 patients. Only 3 patients showed normal OERPs. SAI was significantly reduced in the PD patients with absent OERPs compared with those with present but abnormal OERPs. Neuropsychological examination showed a mild cognitive impairment in 12 out of 13 PD patients with severe olfactory dysfunction, and in 3 out of the 15 patients with borderline olfactory dysfunction. SAI abnormalities and presence of severe olfactory impairment strongly support the hypothesis of cholinergic dysfunction in some patients with PD, who will probably develop a dementia. Longitudinal studies are required to verify whether SAI abnormalities in PD patients with olfactory dysfunction can predict a future severe cognitive decline.

Trigemino-cervical-spinal reflexes after traumatic spinal cord injury.

OBJECTIVE After spinal cord injury (SCI) reorganization of spinal cord circuits occur both above and below the spinal lesion. These functional changes can be determined by assessing electrophysiological recording. We aimed at investigating the trigemino-cervical reflex (TCR) and trigemino-spinal reflex (TSR) responses after traumatic SCI. METHODS TCR and TSR were registered after stimulation of the infraorbital nerve from the sternocleidomastoid, splenius, deltoid, biceps and first dorsal interosseous muscles in 10 healthy subjects and 10 subjects with incomplete cervical SCI. RESULTS In the control subjects reflex responses were registered from the sternocleidomastoid, and splenium muscles, while no responses were obtained from upper limb muscles. In contrast, smaller but clear short latency EMG potentials were recorded from deltoid and biceps muscles in about half of the SCI patients. Moreover, the amplitudes of the EMG responses in the neck muscles were significantly higher in patients than in control subjects. CONCLUSION The reflex responses are likely to propagate up the brainstem and down the spinal cord along the reticulospinal tracts and the propriospinal system. Despite the loss of corticospinal axons, synaptic plasticity in pre-existing pathways and/or formation of new circuits through sprouting processes above the injury site may contribute to the findings of this preliminary study and may be involved in the functional recovery. SIGNIFICANCE Trigemino-cervical-spinal reflexes can be used to demonstrate and quantify plastic changes at brainstem and cervical level following SCI.

Central motor and sensory conduction in patients with hepatic myelopathy

Study design:Experimental neurophysiological study.Objectives:The hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while there are only a few reports of sensory impairment. However, sensory function has been poorly explored in HM. We believe that an electrophysiological assessment of dorsal columns by somatosensory evoked potentials (SEPs) and of cortico-spinal lateral tracts by motor evoked potentials (MEPs) should be of considerable value in the functional evaluation of the spinal cord involvement in patients with HM.Setting:Salzburg (Austria) and Merano (Italy).Methods:Eight patients diagnosed with HM were studied with MEPs and SEPs. Neurological examination revealed different degrees of cortico-spinal tract involvement in all patients and sensory abnormalities in three patients.Results:Central motor conduction to lower limb muscles was abnormal in all patients, while central sensory conduction was abnormal in seven out of the eight patients. Both central motor and sensory conduction to upper limbs are normal in all patients.Conclusion:The main finding is that electrophysiological evidence of central sensory involvement is present in a very high percentage of patients with HM, and that the threshold for electrophysiological abnormalities is below that for clinical manifestations. Therefore, central sensory and motor conduction studies are sensitive methods for detecting, localizing and monitoring spinal cord damage in HM.

Optic nerve sonography in a patient with osteopetrosis.

Osteopetrosis produces abnormally dense and brittle bone that is prone to fracture.1 Cranial nerve dysfunction often occurs as the result of stenosis of foramina at the skull base. The cause of visual disturbances in osteopetrosis may be due to a compressive optic neuropathy from narrowing at the optic canal or may be due to increased intracranial pressure. Optic nerve sonography (US) has been used to identify and monitor intracranial hypertension through the measurement of the optic nerve sheath diameter (ONSD), since increased intracranial pressure of different aetiologies leads to enlargement of the ONSD.2,3 We describe a patient with visual disturbances from osteopetrosis-related optic nerve edema due to enhanced intracranial pressure. A 22-year-woman with osteopetrosis was referred to our hospital complaining of visual disturbances. In particular she noted, since two weeks prior, transient bilateral visual obscurations. The patient was taking the contraceptive pill and was overwight (her body mass index was 28). On examination, visual acuity was 7/10. Pupil, motility, intraocular pressure, and slit lamp examinations were normal. Computerized visual fields analysis showed bilateral blind spot enlargement. There was grade 2 to 3 bilateral optic nerve edema (according to the Modified Frisén Scale)4 with superimposed mild pallor. Magnetic resonance imaging and computed tomography scans showed thickening of the skull, especially at the skull base. A magnetic resonance venography showed no evidence of sinus thrombosis. The lumbar puncture revealed an increased opening pressure of 35 cm H20, but otherwise normal cerebrospinal fluid (cell count, glucose and protein levels). Ultrasound examinations of the eye were carried out with the same procedure previously described.2,3 Transorbital US was carried out in B-mode using a Vivid Seven ultrasound system and a 7-11 MHz linear array transducer (General Electric Healthcare, Milwaukee, WI, USA). The patient was examined in supine position with the upper part of the body and the head elevated to 20-30°. For safety reasons of biomechanical side-effects, the mechanical index (MI) was reduced to 0.2. The probe was placed on the temporal part of the closed upper eyelid using a thick layer of ultrasound gel. The anterior part of the optic nerve was depicted in an axial plane showing the papilla and the optic nerve in its longitudinal course. ONSD was measured 3 mm behind the globe.4 In order to gauge the ONSD, the distance between the external borders of the hyperechogenic area surrounding the optic nerve was quantified. Each bulb was examined three times and means were calculated. Optic Nerve Sonography in a Patient with Osteopetrosis

Effects of intermittent theta burst stimulation on spasticity after spinal cord injury

PURPOSE Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. METHODS In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. RESULTS Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. CONCLUSION These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.

Passive cycling in neurorehabilitation after spinal cord injury: A review

Context/Objective: Passive cycling (PC) may represent a potential alternative neurorehabilitation program for patients who are too weak or medically unstable to repeatedly practice active movements. We review here the most important animal and human studies addressing PC after spinal cord injury (SCI). Methods: A MEDLINE search was performed using following terms: “passive”, “cycling”, “pedaling”, “pedalling”,“spinal cord injury”. Results: Experimental studies revealed that PC modulated spinal reflex and reduced spasticity. PC also reduced autonomic dysreflexia and elicited cardio-protective effects. Increased levels of mRNA for brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-4 were found. In contrast, human studies failed to show an effect of PC on spasticity reduction and did not support its application for prevention of cardiovascular disease-related secondary complications. Conclusion: Available evidence to support the use of PC as standard treatment in patients with SCI is still rather limited. Since it is conceivable that PC motion could elicit sensory inputs to activate cortical structures and induce cortical plasticity changes leading to improved lower limb motor performance, further carefully designed prospective studies in subjects with SCI are needed.