Erik P. Sganzerla

Surgical, Medical, and Hardware Adverse Events in a Series of 141 Patients Undergoing Subthalamic Deep Brain Stimulation for Parkinson Disease

BACKGROUNDnSubthalamic deep brain stimulation has proved significant efficacy in the treatment of Parkinson disease. Adverse events, due to surgical and hardware-related complications, must be clearly addressed to properly balance the cost-effectiveness of the therapy. In addition, limited data exists about medical adverse events after surgery.nnnMETHODSnOne hundred forty-one patients undergoing subthalamic deep brain stimulation for Parkinson disease from 1998 to 2007 were considered. Medical records, operative notes, clinical findings at follow-up and final outcome were accurately recorded to identify surgical- and hardware-related complications, infections and delayed adverse medical events.nnnRESULTSnFive hundred twenty-two surgical procedures were performed, including electrodes positioning and impulse programmable generators implantation and substitutions. Mean follow-up of the patients was 4.6 years (9 months-10 years). Surgical complications were observed in 5.6% of patients, including two hemorrhages (1.4%) and three (2.1%) inabilities to complete the surgical procedure. Medical delayed adverse events affected 1.4% of patients, with a patient having a fatal aspiration pneumonia. Infections were seen in 5.6% of patients; removal of the hardware was necessary in 3.6%. Hardware-adverse events were observed in 7% of patients, generally requiring minor surgery. Direct surgical mortality was 0%; overall mortality was 0.7% and permanent surgical morbidity was 0.7%.nnnCONCLUSIONSnDeep brain stimulation can be regarded as a safe procedure. Mortality and permanent morbidity are very low, and surgical complications are relatively rare. Nevertheless, minor complications are not infrequent; hence the importance of continuous monitoring of the patients during the follow-up period.

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood–brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m2 decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood–brain barrier, might in the future improve the MPS II outcome.

Hemodynamic monitoring of intracranial collateral flow predicts tissue and functional outcome in experimental ischemic stroke

Intracranial collaterals provide residual blood flow to penumbral tissue in acute ischemic stroke and contribute to infarct size variability in humans. In the present study, hemodynamic monitoring of the borderzone territory between the leptomeningeal branches of middle cerebral artery and anterior cerebral artery was compared to lateral middle cerebral artery territory, during common carotid artery occlusion and middle cerebral artery occlusion in rats. The functional performance of intracranial collaterals, shown by perfusion deficit in the territory of leptomeningeal branches either during common carotid artery occlusion or middle cerebral artery occlusion, showed significant variability among animals and consistently predicted infarct size and functional deficit. Our findings indicate that leptomeningeal collateral flow is a strong predictor of stroke severity in rats, similarly to humans. Monitoring of collateral blood flow in experimental stroke is essential for reducing variability in neuroprotection studies and accelerating the development of collateral therapeutics.

Spinal Cord Stimulation for the Treatment of Sensory Symptoms in Advanced Parkinson's Disease

INTRODUCTION Parkinson’s disease (PD) affects more than six million people all over the world (1). The cardinal motor symptoms (i.e., tremor, bradykinesia, and rigidity) are still considered the main diagnostic criteria in diagnosing PD. However, a principal role on the quality of life of the patient is borne by nonmotor symptoms, which remain underestimated and generally undertreated (2). Nonmotor manifestations (NMMs) include mainly mood alterations and psychiatric disorders, cognitive decline, sensory symptoms (e.g., pain and dysesthesias), apathy, sexual difficulties, bowel incontinence, and sleep troubles. The under-recognition of these symptoms has important therapeutic and social implications, as many of NMMs can be successfully treated (1). among NMMs, chronic pain represents one of the most common harms; pain is reported as burning, electrical, commonly joined with parestesias, dysesthesia, and hypoesthesia, resembling the features of“central”pain (3–7). Its physiopathology is not clear at all: an imbalance of the sensorial efferents from basal ganglia to the somatosensory somatomotor primary area (SM1) cortex, due to the dopaminergic circuitry degeneration, has been supposed so far, without any anatomic or functional demonstration; moreover, no L-dopa nor deep brain stimulation (DBS) seems to improve the control of sensory symptoms (8). Spinal cord stimulation (SCS) proved its efficacy in the treatment of complex neuropathic and/or central pain syndromes (9–13): Therefore, we considered to perform SCS in a patient with advanced PD, previously treated with bilateral subthalamic DBS, who developed chronic intractable leg pain. Our aim was to determine if SCS could allow a better control of pain and sensitivity disorders in advanced PD.

Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the thoracic spine

Phosphaturic mesenchymal tumors that cause the paraneoplastic syndrome known as oncogenic osteomalacia are rare. The authors report on the case of a 57-year-old man with a history of osteomalacia and in whom was diagnosed a thoracic spine tumor at the T-4 level. Complete tumor resection was accomplished. The histological diagnosis was phosphaturic mesenchymal tumor (mixed connective tissue variant). After lesion removal, the paraneoplastic syndrome resolved. At the 24-month follow-up, no recurrence of the disease was observed. The clinical presentation, surgical technique, and follow-up in this case were reviewed in detail.

The association of neural axis and craniovertebral junction anomalies with scoliosis in Rubinstein–Taybi syndrome

ObjectRubinstein–Taybi syndrome (RSTS) is a rare condition with characteristic genetic and clinical features. The presence of variable vertebral and neural axis abnormalities has been reported in the literature. We describe the possible association of multiple different spinal anomalies in these patients.ResultsThe radiological exams of two RSTS patients (a female and male of 11 and 13xa0years) have been reviewed. Both patients presented the simultaneous association of craniovertebral junction bony abnormalities (occipito-C1 condyle subluxation and posterior C2–C3 arches fusion), Chiari I malformation, spinal cord syrinx, low-lying conus medullaris, and scoliosis.ConclusionAn association of different spinal cord anomalies is possible in RSTS patients and has to be investigated with a comprehensive neuroimaging study in order to address the proper treatment and prevent the development of neurologic deficits.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (nu2009=u2009118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30u2009min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57u2009mm3 absolute mean difference; pu2009<u20090.001) and higher chance of good functional outcome (OR 4.58, pu2009<u20090.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; pu2009<u20090.001) and lateral (+19.2%; pu2009=u20090.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Severely Symptomatic Craniovertebral Junction Abnormalities in Children

Objectives: The treatment of symptomatic cranio-vertebral junction (CVJ) instability in children affected by CVJ abnormalities is a challenge. A series of severely symptomatic children has been reviewed to understand the controversial long-term effectiveness of the aggressive management of CVJ abnormalities, in terms of clinical improvement, spinal stability and growth. Methods: Three Down syndrome patients, 1 with mucopolysaccharidosis and 1 with os odontoideum (range 3–6 years old) with a CVJ instability determining spinal cord compression with severe neurological deficits (the patients presented at admission a Ranawat III A/III B neurological condition), were consecutively treated at our institution. Medical records, imaging studies, adopted surgical techniques and long-term results were reviewed. Details of the presenting symptoms, clinical and radiological signs were compared to the signs and symptoms at follow-up. Results: The perioperative use of an halo-orthosis, the operative techniques and the timing of rehabilitation were always tailored to the patient’s anatomical features. All the patients showed remarkable neurological improvements, along with construct stability and bone fusion without abnormalities of the developing spine. Conclusions: Considering the effective long-term results, we recommend, even in severely symptomatic children with CVJ abnormalities, a multidisciplinary aggressive tailored treatment of instability with rigid internal fixation.

Bilateral subthalamic deep brain stimulation in a patient with Parkinson's disease who had previously undergone thalamotomy and autologous adrenal grafting in the caudate nucleus: case report

OBJECTIVESubthalamic (Stn) deep brain stimulation (DBS) is a valid surgical therapy for the treatment of severe Parkinsons disease. In recent years, StnDBS has been proposed for patients who previously received other surgical treatments, such as thalamotomy and pallidotomy. Nonetheless, there is no consensus about the indications of DBS in patients who previously underwent surgery. To the best of our knowledge this is the first reported case of a patient treated with DBS after previous thalamotomy and adrenal grafting. CLINICAL PRESENTATIONA 62-year-old man with a long history (more than 30 yr) of Parkinsons disease received unilateral thalamotomy and autologous adrenal graft on two independent occasions. Thalamotomy led to a significant improvement, although limited to the control of contralateral tremor. The autologous adrenal graft was of no benefit. For the subsequent occurrence of L-dopa related dyskinesias and severe “off” periods, the patient was referred to our center for StnDBS. INTERVENTIONThe patient underwent bilateral StnDBS, obtaining a satisfactory improvement of rigidity and bradykinesia on both sides. The 1-year follow-up evaluation showed a 46% improvement in the Unified Parkinsons Disease Rating Scale motor section, along with a noticeable reduction in antiparkinsonian therapy (81%). CONCLUSIONThis case is consistent with previous reports from the literature, suggesting that StnDBS is feasible and safe, even in patients who previously received other surgical treatments for Parkinsons disease, such as thalamotomy or cell grafting.

Cavum veli interpositi: just an anatomical variant or a potentially symptomatic CSF compartmentalization?

Background: The cavum veli interpositi (CVI) usually is a small CSF-containing abnormality of septum pellucidum, asymptomatic and rare after the age of 3 years. When symptomatic, it is large and can be related to psychiatric disorders, syndromic association of mental retardation and seizures or to hydrocephalus. Methods: This is the first reported case of an otherwise healthy pediatric patient with a large CVI experiencing episodes of hypertonic loss of consciousness unrelated to epileptic, cardiologic or psychiatric causes without signs of chronic increase in intracranial pressure (ICP). Results: Supposing a CSF compartmentalization in the CVI as the cause of acute poussés of ICP due to block of CSF pathways and considering the severity of the symptoms, an endoscopic fenestration was performed with a reduction of cyst dimensions. Conclusion: We suggest considering the fenestration of large CVI even in otherwise asymptomatic patients to avoid the risk of CSF compartmentalization with ICP poussés.