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The blood-brain barrier (BBB) forms an important interface between the central nervous system and the general circulation. It is vested with an important barrier function that involves both passive structural barriers and active transport processes that ensure maintenance of the specialized environment requisite for normal neural function. Although it has been studied for many decades, findings including the description of the glymphatic circulation and of a lymphatic system at the brain periphery have shed light on the complex functioning of the BBB. Here we review an up-to-date description of the normal structure and function of the BBB on which there is much exciting information. We then review the somewhat more fragmented information on the impact of type 2 diabetes (T2D) or insulin resistance (IR) on BBB structure and function. Considering that hyperglycemia per se appears to be a major driver for endothelial cell injury and dysfunction in both T2D and type 1 diabetes (T1D), we include some results of studies with T1D animal models. We recognize that much of the work previously done relating to the impact of hyperglycemia as seen in T2D and T1D on the BBB was performed before new information on the BBB structure and its relationship to the cerebrospinal fluid circulation. Much work remains to be done to clarify the impact of diabetes mellitus or IR on BBB structure and function. Urgency for such work is increased by the recognition of the clinical association between T2D/IR and an enhanced risk of early cognitive decline.

Hydrocephalus (HC) is classically defined as dynamic imbalance between the production and absorption of cerebrospinal fluid (CSF) leading to enlarged ventricles. Potential causative factors include various brain disorders like tumors causing obstruction of CSF flow within the ventricular system or the subarachnoid space. Classification of HC is based on the site of CSF flow obstruction guiding optimal treatment, with endoscopic third ventriculostomy in intraventricular obstruction and CSF shunt in communicating HC. Another clinically relevant classification is acute and chronic; the most frequent chronic form is idiopathic normal-pressure hydrocephalus (iNPH). The reported incidence of HC varies according to the study population and classification used. The incidence of congenital HC is approximately 0.4-0.6/1,000 newborns and the annual incidence of iNPH varies from 0.5/100,000 to 5.5/100,000. Radiologically, ventricular dilatation may be nonspecific, and differentiation of iNPH from other neurodegenerative diseases may be ambiguous. There are no known specific microscopic findings of HC but a systematic neuropathologic examination is needed to detect comorbid diseases and possible etiologic factors of HC. Depending on the etiology of HC, there are several nonspecific signs potentially to be seen.

Activity-related headaches can be brought on by Valsalva maneuvers (“cough headache”), prolonged exercise (“exertional headache”), and sexual excitation (“orgasmic headache”). These headaches account for 1–2% of the consultations due to headache in a general neurological department. These entities are a challenging diagnostic problem as they can be primary or secondary and as their etiologies differ depending on the headache type. About 50% of patients with cough headache will show no demonstrable etiology, while the other half will be secondary to structural lesions, mostly a Chiari type I malformation at the foramen magnum level. As compared to the primary variety, secondary cough headache begins earlier (average 40 versus 60 years), is located posteriorly, lasts longer (years versus months), is associated with posterior fossa symptoms/signs, and does not respond to indomethacin. Patients with secondary cough headache show difficulties in cerebrospinal fluid circulation in the foramen magnum region in dynamic magnetic resonance imaging studies and preoperative plateau waves, which disappear after posterior fossa reconstruction. Headaches provoked by physical exercise and sexual headache have many points in common. In contrast to cough headache, secondary cases are rare, and sentinel subarachnoid bleeding is the most frequent etiology. The mean age at onset for primary headaches provoked by physical exercise and sexual activity is similar (40 years); they share clinical characteristics (bilateral, pulsating) and respond to beta-blockers. In conclusion, provoked headaches account for a low proportion of headache consultations. Cough headache is a different condition when compared to headache due to physical exercise and sexual activity, which are clinical variants of the same entity.