Segmental innervation of the Göttingen minipig hind body. An electrophysiological study.

The Göttingen minipig is being used increasingly in biomedical research. The anatomical structure of the porcine peripheral nervous system has been extensively characterized, but no equivalent to the dermatome map, which is so valuable in human neurophysiological research, has been created. We characterized the medullar segmental skin and muscle innervations of the minipig hind body, using neurophysiological methodology. Six adult minipigs underwent unilateral laminectomy from L2 to S3, exposing the nerve roots. The skin of the hind part of the body was divided into 36 predefined fields, based on anatomical landmarks for consistent reproducibility. We recorded the evoked potential in each exposed nerve root L2-S3 for cutaneous stimulation of each skin field, mapping the sensory innervation of the entire hind body. We subsequently recorded the motor response in seven predefined muscles during sequential stimulation of the L2-S3 nerve roots. We obtained a clear sensory evoked potential in the nerve roots during stimulation of the skin fields, allowing us to map the sensory innervation of the minipig hind body. Neurophysiological data from skin stimulation and muscle recordings enabled us to map the sensory innervation of the Göttingen minipig hind body and provide information about muscular innervation. The skin fields were sensory innervated by more than one root. The muscles each had one dominant root with minor contribution from neighboring roots. This is consistent with experimental data from human studies.

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

Objective: To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Methods: Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Results: Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. Conclusion: The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

Subarachnoid haemorrhage is a rare cause of headache and status epilepticus in children.

New onset of seizures in children presenting with status epilepticus (SE) are rarely caused by intracranial aneurysms and haemorrhage, and the diagnosis is therefore challenging. This case report presents a ten-year-old healthy girl presenting with SE preceded by headache for two weeks. A CT-scan showed a subarachnoidal haemorrhage from a cerebral aneurysm. Intracranial pathology should be considered a differential diagnosis when receiving a child with new onset of seizures and SE. Early neuroimaging should be performed for correct treatment to be initiated without delay.

Pirouetting pigs: A large non-primate animal model based on unilateral 6-hydroxydopamine lesioning of the nigrostriatal pathway.

INTRODUCTION: The rotating 6-hydroxydopamine (6-OHDA) rat model has long been important when developing new treatment strategies for Parkinson's disease (PD). Similar non-human primate models have been developed for translational research purposes as large animal models are required by regulatory bodies as an intermediate "phase 0" trial step. However, experimental research in non-human primates encounters several economical and regulatory issues, which may be avoided by the alternative use of pigs as a large animal model for experimental brain research. OBJECTIVE: The primary aim of this study was to examine if unilateral injections of 6-OHDA into the Göttingen minipig nigrostriatal pathway would lead to dopaminergic imbalance and rotational behavior similar to the 6-OHDA unilateral symptomatic model of PD created in other species. The secondary aim was to attempt to verify the rotational behavior as a parkinsonian symptom using subthalamic deep brain stimulation (STN-DBS) to minimize the elicited rotational pattern. MATERIALS AND METHODS: Using an MRI-based stereotactic procedure, ten female Göttingen minipigs were injected unilaterally with 6-OHDA in the nigrostriatal pathway. Postoperatively, an MRI was performed, and the animals were injected with amphetamine and apomorphine and observed for rotational behavior. After a survival period of three months the brains were removed and immunohistochemically stained for tyrosine hydroxylase (TH). One week before sacrifice two animals had DBS electrodes unilaterally implanted in the subthalamic nucleus and various stimulation protocols were conducted during amphetamine challenge. RESULTS: As expected most animals rotated towards the side of the lesion when given amphetamine (3.5-4.0 mg/kg), whereas the predicted opposite response to apomorphine were much harder to reproduce. T1- and T2-weighted postoperative MRI could demonstrate the size and the location of the 6-OHDA injection. Postmortem TH-staining of the final two animals receiving a medial and a lateral injection of 25 µL of 6-OHDA (8 µg/µL, injection rate 5 µL/min) into the diencephalic nigrostriatal pathway showed a prominent unilateral decrease in TH-staining of the substantia nigra pars compacta, the ventral tegmental area and the nigrostriatal pathway on the lesioned side. These two animals displayed spontaneous rotational behavior toward the lesioned side for the first 2-3 days postoperatively, and this behavior could later on be reelicited by amphetamine and attenuated by ipsilateral STN-DBS. CONCLUSION: Female Göttingen minipigs are susceptible to unilateral dopaminergic degeneration when properly injected unilaterally with sufficient amounts of 6-OHDA in the nigrostriatal pathway. The location of the 6-OHDA injections and thus the accuracy of the employed stereotaxy can be verified in vivo using MRI postoperatively. The injected minipigs display unilateral parkinsonism with a well-defined rotational response to amphetamine that may be ameliated by STN-DBS performed on the lesioned side. The response to apomorphine was, however, not consistent, illustrating that further work on this promising non-primate large animal model is needed, before it is fully similar to the established 6-OHDA models in other species.